NCBI Conserved Domain Search

aspartate kinase; Reviewed

Pssm-ID: 235843 [Multi-domain] Cd Length: 404 Bit Score: 189.56 E-value: 3.88e-59

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 705441832  19 EAPVISGVAHDRTEALATLRGVPNEPGMAAKVFTQLAEAGVNVDMIVQAGASTGTADISFTVPETTVRSVQEVLEVKQDE 98
Cdd:PRK06635 249 EQPVVTGIAFDKDEAKVTVVGVPDKPGIAAQIFGALAEANINVDMIVQNVSEDGKTDITFTVPRDDLEKALELLEEVKDE 328

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 705441832  99 LGYQAFEINNNVGKVAVVGVGMKTHSGVAAKFFNALSEHGINVLMISTSEIRIAALVPLPELDDAVRALHTAYGLD 174
Cdd:PRK06635 329 IGAESVTYDDDIAKVSVVGVGMRSHPGVAAKMFEALAEEGINIQMISTSEIKISVLIDEKYLELAVRALHEAFGLD 404

Aspartate kinase [Amino acid transport and metabolism]; Aspartate kinase is part of the Pathway/BioSystem: Lysine biosynthesis

Pssm-ID: 440293 [Multi-domain] Cd Length: 407 Bit Score: 156.01 E-value: 3.50e-46

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 705441832  19 EAPVISGVAHDRTEALATLRGVP--NEPGMAAKVFTQLAEAGVNVDMIVQagaSTGTADISFTVPETTVRSVQEVLEVKQ 96
Cdd:COG0527  249 EGPVVKGIASDKDIALITVSGVPmvDEPGFAARIFSALAEAGINVDMISQ---SSSETSISFTVPKSDLEKALEALEEEL 325

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 705441832  97 DELGYQAFEINNNVGKVAVVGVGMKTHSGVAAKFFNALSEHGINVLMIST--SEIRIAALVPLPELDDAVRALHTAYGLD 174
Cdd:COG0527  326 KLEGLEEVEVEEDLAKVSIVGAGMRSHPGVAARMFSALAEAGINIRMISQgsSEISISVVVDEEDAEKAVRALHEAFFLD 405


                 ..
gi 705441832 175 AD 176
Cdd:COG0527  406 KE 407

aspartate kinase; Provisional

Pssm-ID: 236018 [Multi-domain] Cd Length: 587 Bit Score: 149.68 E-value: 1.40e-42

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 705441832  17 GPEAPVISGVAHDRTEALATLRGVPNEPGMAAKVFTQLAEAGVNVDMIVQA--GASTGTADISFTVPETTVRSVQEVLEV 94
Cdd:PRK07431 424 GQDEPEVRGVALDRNQAQLAIRNVPDRPGMAASIFGALAEANISVDMIVQSqrCRSDGTRDISFTVPKEDREAAQKVLRE 503

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 705441832  95 KQDELGYQAFEINNNVGKVAVVGVGMKTHSGVAAKFFNALSEHGINVLMISTSEIRIAALVPLPELDDAVRALHTAYGLD 174
Cdd:PRK07431 504 LAKQLPGAEVEDGPAIAKVSIVGAGMPGTPGVAARMFRALADAGINIEMIATSEIRTSCVVAEDDGVKALQAVHQAFGLA 583


                 ...
gi 705441832 175 ADR 177
Cdd:PRK07431 584 GEE 586

aspartate kinase; Provisional

Pssm-ID: 236018 [Multi-domain] Cd Length: 587 Bit Score: 131.96 E-value: 5.02e-36

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 705441832  20 APVISGVAHDRTEALATLRGVPNEPGMAAKVFTQLAEAGVNVDMIVQAGASTGTADISFTVPETTVRSVQEVLEVKQDEL 99
Cdd:PRK07431 258 GKPVDGVELDEDQAKVALLRVPDRPGIAAQLFEELAAQGVNVDLIIQSIHEGNSNDIAFTVAENELKKAEAVAEAIAPAL 337

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 705441832 100 GYQAFEINNNVGKVAVVGVGMKTHSGVAAKFFNALSEHGINVLMISTSEIRIAALVPLPELDDAVRALHTAYGLDADRIE 179
Cdd:PRK07431 338 GGAEVLVETNVAKLSISGAGMMGRPGIAAKMFDTLAEAGINIRMISTSEVKVSCVIDAEDGDKALRAVCEAFELEDSQIE 417


                 .
gi 705441832 180 A 180
Cdd:PRK07431 418 I 418

aspartate kinase; Aspartate kinase catalyzes a first step in the biosynthesis from Asp of Lys (and its precursor diaminopimelate), Met, and Thr. In E. coli, a distinct isozyme is inhibited by each of the three amino acid products. The Met-sensitive (I) and Thr-sensitive (II) forms are bifunctional enzymes fused to homoserine dehydrogenases and form homotetramers, while the Lys-sensitive form (III) is a monofunctional homodimer.The Lys-sensitive enzyme of Bacillus subtilis resembles the E. coli form but is an alpha 2/beta 2 heterotetramer, where the beta subunit is translated from an in-phase alternative initiator at Met-246. This may be a feature of a number of closely related forms, including a paralog from B. subtilis. [Amino acid biosynthesis, Aspartate family]

Pssm-ID: 273201 [Multi-domain] Cd Length: 441 Bit Score: 116.30 E-value: 6.03e-31

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 705441832   18 PEAPVISGVAHDRTEALATLRGVP-NEPGMAAKVFTQLAEAGVNVDMIVQagaSTGTADISFTVPETTVRSVQEVLEVKQ 96
Cdd:TIGR00657 288 MEEPIVKGLSLDRNQARVTVSGLGmKGPGFLARVFGALAEAGINVDLISQ---SSSETSISFTVDKEDADQAKELLKSEL 364

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 705441832   97 DELGYQAFEINNNVGKVAVVGVGMKTHSGVAAKFFNALSEHGINVLMISTSEIRIAALVPLPELDDAVRALHTAYGL 173
Cdd:TIGR00657 365 NLSALSRVEVEKGLAKVSLVGAGMKSAPGVASKIFEALAQNGINIEMISSSEINISFVVDEKDAEKAVRLLHNALFE 441

ACT domains of the lysine-sensitive aspartokinase isoenzyme AKII of Bacillus subtilis (BS) strain 168 and related proteins; This CD includes the N-terminal of the two ACT domains of the lysine-sensitive aspartokinase isoenzyme AKII of Bacillus subtilis (BS) strain 168, and the lysine plus threonine-sensitive aspartokinase of Corynebacterium glutamicum, and related sequences. In B. subtilis 168, the regulation of the diaminopimelate (Dap)-lysine biosynthetic pathway involves dual control by Dap and lysine, effected through separate Dap- and lysine-sensitive aspartokinase isoenzymes. The B. subtilis 168 AKII is induced by methionine and repressed and inhibited by lysine. Although Corynebacterium glutamicum is known to contain a single aspartokinase, both the succinylase and dehydrogenase variant pathways of DAP-lysine synthesis operate simultaneously in this organism. In corynebacteria and other various Gram-positive bacteria, the DAP-lysine pathway is feedback regulated by the concerted action of lysine and threonine. Conserved residues in the ACT domains have been shown to be involved in this concerted feedback inhibition. Also included in this CD are the aspartokinases of the extreme thermophile, Thermus thermophilus HB27, the Gram-negative obligate methylotroph, Methylophilus methylotrophus AS1, and those single aspartokinases found in Pseudomonas aeruginosa, C. glutamicum, and Amycolatopsis lactamdurans. B. subtilis 168 AKII, and the C. glutamicum, Streptomyces clavuligerus and A. lactamdurans aspartokinases are described as tetramers consisting of two alpha and two beta subunits; the alpha (44 kD) and beta (18 kD) subunits formed by two in-phase overlapping polypeptides. This CD includes the first ACT domain C-terminal to the AK catalytic domain of the alpha subunit and the first ACT domain of the beta subunit that lacks the AK catalytic domain. Unlike the C. glutamicum AK beta subunit, which is involved in feedback regulation, the B. subtilis AKII beta subunit is not. Cyanobacteria aspartokinases are unique to this CD and they have a unique domain architecture with two tandem pairs of ACT domains, C-terminal to the catalytic AK domain. In this CD, the first and third cyanobacteria AK ACT domains are present. Members of this CD belong to the superfamily of ACT regulatory domains.

Pssm-ID: 153185 Cd Length: 75 Bit Score: 94.13 E-value: 9.97e-26

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 705441832  32 EALATLRGVPNEPGMAAKVFTQLAEAGVNVDMIVQAGASTGTADISFTVPETTVRSVQEVLEVKQDELGYQAFEI 106
Cdd:cd04913    1 QAKITLRGVPDKPGVAAKIFGALAEANINVDMIVQNVSRDGTTDISFTVPKSDLKKALAVLEKLKKELGAEEVEY 75

ACT domains of the lysine-sensitive aspartokinase isoenzyme AKII and related proteins; This CD includes the N-terminal of the two ACT domains of the lysine-sensitive aspartokinase isoenzyme AKII of Bacillus subtilis (BS) strain 168, and the lysine plus threonine-sensitive aspartokinase of Corynebacterium glutamicum, as well as, the first and third, of four, ACT domains present in cyanobacteria AK. Also included are the N-terminal of the two ACT domains of the diaminopimelate-sensitive aspartokinase isoenzyme AKI found in Bacilli (Bacillus subtilis strain 168), Clostridia, and Actinobacteria bacterial species. Members of this CD belong to the superfamily of ACT regulatory domains.

Pssm-ID: 153163 [Multi-domain] Cd Length: 61 Bit Score: 81.83 E-value: 4.75e-21

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 705441832  36 TLRGVPNEPGMAAKVFTQLAEAGVNVDMIVQAGASTGTADISFTVPETTVRSVQEVLE 93
Cdd:cd04891    4 TIKGVPDKPGVAAKIFSALAEAGINVDMIVQSVSRGGTTDISFTVPKSDLEKALAILE 61

ACT domains of the lysine-sensitive aspartokinase isoenzyme AKII of Bacillus subtilis (BS) strain 168 and related domains; This CD includes the C-terminal of the two ACT domains of the lysine-sensitive aspartokinase isoenzyme AKII of Bacillus subtilis (BS) strain 168, and the lysine plus threonine-sensitive aspartokinase of Corynebacterium glutamicum, as well as, the second and fourth, of four, ACT domains present in cyanobacteria AK. Also included are the C-terminal of the two ACT domains of the diaminopimelate-sensitive aspartokinase isoenzyme AKI found in Bacilli (B. subtilis strain 168), Clostridia, and Actinobacteria bacterial species. Members of this CD belong to the superfamily of ACT regulatory domains.

Pssm-ID: 153195 Cd Length: 63 Bit Score: 79.48 E-value: 3.73e-20

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....
gi 705441832 120 MKTHSGVAAKFFNALSEHGINVLMISTSEIRIAALVPLPELDDAVRALHTAYGL 173
Cdd:cd04923   10 MRSHPGVAAKMFKALAEAGINIEMISTSEIKISCLVDEDDAEKAVRALHEAFEL 63

ACT domains of the lysine-sensitive, aspartokinase (AK) isoenzyme AKII of Bacillus subtilis (BS) strain 168 and related domains; This CD includes the C-terminal of the two ACT domains of the lysine-sensitive, aspartokinase (AK) isoenzyme AKII of Bacillus subtilis (BS) strain 168, and the lysine plus threonine-sensitive aspartokinase of Corynebacterium glutamicum, and related sequences. In B. subtilis strain 168, the regulation of the diaminopimelate (Dap)-lysine biosynthetic pathway involves dual control by Dap and lysine, effected through separate Dap- and lysine-sensitive AK isoenzymes. The B. subtilis strain 168 AKII is induced by methionine and repressed and inhibited by lysine. Although C. glutamicum is known to contain a single AK, both the succinylase and dehydrogenase variant pathways of DAP-lysine synthesis operate simultaneously in this organism. In corynebacteria and other various Gram-positive bacteria, the DAP-lysine pathway is feedback regulated by the concerted action of lysine and threonine. Conserved residues in the ACT domains have been shown to be involved in this concerted feedback inhibition. Also included in this CD are the AKs of the extreme thermophile, Thermus thermophilus HB27, the Gram-negative obligate methylotroph, Methylophilus methylotrophus AS1, and those single AKs found in Pseudomons, C. glutamicum, and Amycolatopsis lactamdurans. B. subtilis strain 168 AKII, and the C. glutamicum, Streptomyces clavuligerus and A. lactamdurans AKs are described as tetramers consisting of two alpha and two beta subunits; the alpha (44 kD) and beta (18 kD) subunits formed by two in-phase overlapping polypeptides. This CD includes the second ACT domain C-terminal to the AK catalytic domain of the alpha subunit and the second ACT domain of the beta subunit that lacks the AK catalytic domain. Unlike the C. glutamicum AK beta subunit, which is involved in feedback regulation, the B. subtilis AKII beta subunit is not. Cyanobacteria AKs are unique to this CD and they have a unique domain architecture with two tandem pairs of ACT domains, C-terminal to the catalytic AK domain. In this CD, the second and fourth cyanobacteria AK ACT domains are present. Members of this CD belong to the superfamily of ACT regulatory domains.

Pssm-ID: 153208 Cd Length: 63 Bit Score: 79.11 E-value: 4.93e-20

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....
gi 705441832 120 MKTHSGVAAKFFNALSEHGINVLMISTSEIRIAALVPLPELDDAVRALHTAYGL 173
Cdd:cd04936   10 MRSHPGVAAKMFEALAEAGINIEMISTSEIKISCLIDEDDAEKAVRALHEAFEL 63

aspartate kinase; Provisional

Pssm-ID: 235773 [Multi-domain] Cd Length: 465 Bit Score: 80.74 E-value: 4.75e-18

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 705441832  44 PGMAAKVFTQLAEAGVNVDMIVQagaSTGTADISFTVPETTVRSVQEVLEVKQDELGYQAFEINNNVGKVAVVGVGMKTH 123
Cdd:PRK06291 335 PGTAARIFSALAEEGVNVIMISQ---GSSESNISLVVDEADLEKALKALRREFGEGLVRDVTFDKDVCVVAVVGAGMAGT 411

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|...
gi 705441832 124 SGVAAKFFNALSEHGINVLMIS--TSEIRIAALVPLPELDDAVRALHTAYGLD 174
Cdd:PRK06291 412 PGVAGRIFSALGESGINIKMISqgSSEVNISFVVDEEDGERAVKVLHDEFILG 464

bifunctional aspartokinase I/homoserine dehydrogenase I; Provisional

Pssm-ID: 181856 [Multi-domain] Cd Length: 819 Bit Score: 77.50 E-value: 8.29e-17

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 705441832  44 PGMAAKVFTQLAEAGVNVDMIVQAGA--StgtadISFTVPETTVRSVQEVL------EVKQDELgyQAFEINNNVGKVAV 115
Cdd:PRK09436 329 VGMASRVFAALSRAGISVVLITQSSSeyS-----ISFCVPQSDAAKAKRALeeefalELKEGLL--EPLEVEENLAIISV 401

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 705441832 116 VGVGMKTHSGVAAKFFNALSEHGINVLMIS--TSEIRIAALVPLPELDDAVRALH 168
Cdd:PRK09436 402 VGDGMRTHPGIAAKFFSALGRANINIVAIAqgSSERSISVVIDNDDATKALRACH 456

ACT domains C-terminal to the catalytic domain of aspartokinase (AK; 4-L-aspartate-4-phosphotransferase); This CD includes the second of two ACT domains C-terminal to the catalytic domain of aspartokinase (AK; 4-L-aspartate-4-phosphotransferase). The exception in this group, is the inclusion of the first ACT domain of the bifunctional aspartokinase - homoserine dehydrogenase-like enzyme group (ACT_AKi-HSDH-ThrA-like_1) which includes the monofunctional, threonine-sensitive, aspartokinase found in Methanococcus jannaschii and other related archaeal species. AK catalyzes the conversion of aspartate and ATP to aspartylphosphate and ADP. AK is the first enzyme in the pathway of the biosynthesis of the aspartate family of amino acids (lysine, threonine, methionine, and isoleucine) and the bacterial cell wall component, meso-diaminopimelate. One mechanism for the regulation of this pathway is by the production of several isoenzymes of AK with different repressors and allosteric inhibitors. Pairs of ACT domains are proposed to specifically bind amino acids leading to allosteric regulation of the enzyme. In Escherichia coli (EC), three different AK isoenzymes are regulated specifically by lysine, methionine, and threonine. AK-HSDHI (ThrA) and AK-HSDHII (MetL) are bifunctional enzymes that consist of an N-terminal AK and a C-terminal homoserine dehydrogenase (HSDH). ThrA and MetL are involved in threonine and methionine biosynthesis, respectively. The third isoenzyme, AKIII (LysC), is monofunctional and is involved in lysine synthesis. The three Bacillus subtilis (BS) isoenzymes, AKI (DapG), AKII (LysC), and AKIII (YclM), are feedback inhibited by meso-diaminopimelate, lysine, and lysine plus threonine, respectively. The E. coli lysine-sensitive AK is described as a homodimer, whereas, the B. subtilis lysine-sensitive AK is described as is a heterodimeric complex of alpha- and beta- subunits that are formed from two in-frame overlapping genes. A single AK enzyme type has been described in Pseudomonas, Amycolatopsis, and Corynebacterium, and apparently, unique to cyanobacteria, are AKs with two tandem pairs of ACT domains, C-terminal to the catalytic domain. The fungal aspartate pathway is regulated at the AK step, with L-Thr being an allosteric inhibitor of the Saccharomyces cerevisiae AK (Hom3). At least two distinct AK isoenzymes can occur in higher plants, a monofunctional lysine-sensitive isoenzyme, which is involved in the overall regulation of the pathway and can be synergistically inhibited by S-adenosylmethionine. The other isoenzyme is a bifunctional, threonine-sensitive AK-HSDH protein. Also included in this CD are the ACT domains of the Methylomicrobium alcaliphilum AK; the first enzyme of the ectoine biosynthetic pathway found in this bacterium and several other halophilic/halotolerant bacteria. Members of this CD belong to the superfamily of ACT regulatory domains.

Pssm-ID: 153164 [Multi-domain] Cd Length: 65 Bit Score: 64.06 E-value: 3.06e-14

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 705441832 120 MKTHSGVAAKFFNALSEHGINVLMIST--SEIRIAALVPLPELDDAVRALHTAYGL 173
Cdd:cd04892   10 MRGTPGVAARIFSALAEAGINIIMISQgsSEVNISFVVDEDDADKAVKALHEEFFL 65

ACT domains C-terminal to the catalytic domain of aspartokinase (AK; 4-L-aspartate-4-phosphotransferase); This CD includes each of two ACT domains C-terminal to the catalytic domain of aspartokinase (AK; 4-L-aspartate-4-phosphotransferase). Typically, AK consists of two ACT domains in a tandem repeat, but the second ACT domain is inserted within the first, resulting in, what is normally the terminal beta strand of ACT2, formed from a region N-terminal of ACT1. AK catalyzes the conversion of aspartate and ATP to aspartylphosphate and ADP. Aspartokinase is the first enzyme in the pathway of the biosynthesis of the aspartate family of amino acids (lysine, threonine, methionine, and isoleucine) and the bacterial cell wall component, meso-diaminopimelate. One mechanism for the regulation of this pathway is by the production of several isoenzymes of aspartokinase with different repressors and allosteric inhibitors. Pairs of ACT domains are proposed to specifically bind amino acids leading to allosteric regulation of the enzyme. In Escherichia coli (EC), three different aspartokinase isoenzymes are regulated specifically by lysine, methionine, and threonine. AK-HSDHI (ThrA) and AK-HSDHII (MetL) are bifunctional enzymes that consist of an N-terminal AK and a C-terminal homoserine dehydrogenase (HSDH). ThrA and MetL are involved in threonine and methionine biosynthesis, respectively. The third isoenzyme, AKIII (LysC), is monofunctional and is involved in lysine synthesis. The three Bacillus subtilis (BS) isoenzymes, AKI (DapG), AKII (LysC), and AKIII (YclM), are feedback inhibited by meso-diaminopimelate, lysine, and lysine plus threonine, respectively. The E. coli lysine-sensitive AK is described as a homodimer, whereas, the B. subtilis lysine-sensitive AK is described as is a heterodimeric complex of alpha- and beta- subunits that are formed from two in-frame overlapping genes. A single AK enzyme type has been described in Pseudomonas, Amycolatopsis, and Corynebacterium, and apparently, unique to cyanobacteria, are aspartokinases with two tandem pairs of ACT domains, C-terminal to the catalytic domain. The fungal aspartate pathway is regulated at the AK step, with L-Thr being an allosteric inhibitor of the Saccharomyces cerevisiae AK (Hom3). At least two distinct AK isoenzymes can occur in higher plants, a monofunctional lysine-sensitive isoenzyme, which is involved in the overall regulation of the pathway and can be synergistically inhibited by S-adenosylmethionine. The other isoenzyme is a bifunctional, threonine-sensitive AK-HSDH protein. Also included in this AK family CD are the ACT domains of the Methylomicrobium alcaliphilum AK; the first enzyme of the ectoine biosynthetic pathway found in this bacterium and several other halophilic/halotolerant bacteria. Members of this CD belong to the superfamily of ACT regulatory domains.

Pssm-ID: 153140 [Multi-domain] Cd Length: 60 Bit Score: 60.97 E-value: 5.06e-13

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 705441832  33 ALATLRGVP--NEPGMAAKVFTQLAEAGVNVDMIVQagaSTGTADISFTVPETTVRSVQEVLE 93
Cdd:cd04868    1 AKVSIVGVGmrGTPGVAAKIFSALAEAGINVDMISQ---SESEVNISFTVDESDLEKAVKALH 60

ACT domains C-terminal to the catalytic domain of aspartokinase (AK; 4-L-aspartate-4-phosphotransferase); This CD includes each of two ACT domains C-terminal to the catalytic domain of aspartokinase (AK; 4-L-aspartate-4-phosphotransferase). Typically, AK consists of two ACT domains in a tandem repeat, but the second ACT domain is inserted within the first, resulting in, what is normally the terminal beta strand of ACT2, formed from a region N-terminal of ACT1. AK catalyzes the conversion of aspartate and ATP to aspartylphosphate and ADP. Aspartokinase is the first enzyme in the pathway of the biosynthesis of the aspartate family of amino acids (lysine, threonine, methionine, and isoleucine) and the bacterial cell wall component, meso-diaminopimelate. One mechanism for the regulation of this pathway is by the production of several isoenzymes of aspartokinase with different repressors and allosteric inhibitors. Pairs of ACT domains are proposed to specifically bind amino acids leading to allosteric regulation of the enzyme. In Escherichia coli (EC), three different aspartokinase isoenzymes are regulated specifically by lysine, methionine, and threonine. AK-HSDHI (ThrA) and AK-HSDHII (MetL) are bifunctional enzymes that consist of an N-terminal AK and a C-terminal homoserine dehydrogenase (HSDH). ThrA and MetL are involved in threonine and methionine biosynthesis, respectively. The third isoenzyme, AKIII (LysC), is monofunctional and is involved in lysine synthesis. The three Bacillus subtilis (BS) isoenzymes, AKI (DapG), AKII (LysC), and AKIII (YclM), are feedback inhibited by meso-diaminopimelate, lysine, and lysine plus threonine, respectively. The E. coli lysine-sensitive AK is described as a homodimer, whereas, the B. subtilis lysine-sensitive AK is described as is a heterodimeric complex of alpha- and beta- subunits that are formed from two in-frame overlapping genes. A single AK enzyme type has been described in Pseudomonas, Amycolatopsis, and Corynebacterium, and apparently, unique to cyanobacteria, are aspartokinases with two tandem pairs of ACT domains, C-terminal to the catalytic domain. The fungal aspartate pathway is regulated at the AK step, with L-Thr being an allosteric inhibitor of the Saccharomyces cerevisiae AK (Hom3). At least two distinct AK isoenzymes can occur in higher plants, a monofunctional lysine-sensitive isoenzyme, which is involved in the overall regulation of the pathway and can be synergistically inhibited by S-adenosylmethionine. The other isoenzyme is a bifunctional, threonine-sensitive AK-HSDH protein. Also included in this AK family CD are the ACT domains of the Methylomicrobium alcaliphilum AK; the first enzyme of the ectoine biosynthetic pathway found in this bacterium and several other halophilic/halotolerant bacteria. Members of this CD belong to the superfamily of ACT regulatory domains.

Pssm-ID: 153140 [Multi-domain] Cd Length: 60 Bit Score: 58.66 E-value: 3.85e-12

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|.
gi 705441832 120 MKTHSGVAAKFFNALSEHGINVLMISTS--EIRIAALVPLPELDDAVRALH 168
Cdd:cd04868   10 MRGTPGVAAKIFSALAEAGINVDMISQSesEVNISFTVDESDLEKAVKALH 60

ACT domain; The ACT domain is a structural motif of 70-90 amino acids that functions in the control of metabolism, solute transport and signal transduction. They are thus found in a variety of different proteins in a variety of different arrangements. In mammalian phenylalanine hydroxylase the domain forms no contacts but promotes an allosteric effect despite the apparent lack of ligand binding.

Pssm-ID: 433519 [Multi-domain] Cd Length: 65 Bit Score: 52.92 E-value: 5.19e-10

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*.
gi 705441832  123 HSGVAAKFFNALSEHGINVLMISTsEIRIAALVPLPELDDAVRALH 168
Cdd:pfam13840  20 VPGVVAKLTSPLAEAGISIFQISS-YTTDYVLVPEEDLEKAVRALH 64

aspartate kinase III; Validated

Pssm-ID: 236376 [Multi-domain] Cd Length: 448 Bit Score: 54.83 E-value: 4.26e-09

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 705441832  45 GMAAKVFTQLAEAGVNVDMIvqagaSTGTADISFTVPETTVRSVQEVLEVKQ--DELGYQAF-EINNNVGKVAVVGVGMK 121
Cdd:PRK09084 321 GFLAEVFGILARHKISVDLI-----TTSEVSVSLTLDTTGSTSTGDTLLTQAllTELSQLCRvEVEEGLALVALIGNNLS 395

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*....
gi 705441832 122 THSGVAAKFFNALSEHgiNVLMIS--TSEIRIAALVPLPELDDAVRALH 168
Cdd:PRK09084 396 KACGVAKRVFGVLEPF--NIRMICygASSHNLCFLVPESDAEQVVQALH 442

ACT domains of the bifunctional enzyme aspartokinase (AK) - homoserine dehydrogenase (HSDH); This CD includes the first of two ACT domains of the bifunctional enzyme aspartokinase (AK) - homoserine dehydrogenase (HSDH). The ACT domains are positioned between the N-terminal catalytic domain of AK and the C-terminal HSDH domain found in bacteria (Escherichia coli (EC) ThrA) and higher plants (Zea mays AK-HSDH). AK and HSDH are the first and third enzymes in the biosynthetic pathway of the aspartate family of amino acids. AK catalyzes the phosphorylation of Asp to P-aspartyl phosphate. HSDH catalyzes the NADPH-dependent conversion of Asp 3-semialdehyde to homoserine. HSDH is the first committed reaction in the branch of the pathway that leads to Thr and Met. In E. coli, ThrA is subject to allosteric regulation by the end product L-threonine and the native enzyme is reported to be tetrameric. As with bacteria, plant AK and HSDH are feedback inhibited by pathway end products. Maize AK-HSDH is a Thr-sensitive 180-kD enzyme. Arabidopsis AK-HSDH is an alanine-activated, threonine-sensitive enzyme whose ACT domains were shown to be involved in allosteric activation. Also included in this CD is the first of two ACT domains of a tetrameric, monofunctional, threonine-sensitive, AK found in Methanococcus jannaschii and other related archaeal species. Members of this CD belong to the superfamily of ACT regulatory domains.

Pssm-ID: 153193 [Multi-domain] Cd Length: 80 Bit Score: 49.13 E-value: 2.29e-08

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 705441832 120 MKTHSGVAAKFFNALSEHGINVLMIS--TSEIRIAALVPLPELDDAVRALHTAYGLD 174
Cdd:cd04921   11 MVGVPGIAARIFSALARAGINVILISqaSSEHSISFVVDESDADKALEALEEEFALE 67

ACT domains of the bifunctional enzyme aspartokinase (AK) - homoserine dehydrogenase (HSDH); This CD includes the first of two ACT domains of the bifunctional enzyme aspartokinase (AK) - homoserine dehydrogenase (HSDH). The ACT domains are positioned between the N-terminal catalytic domain of AK and the C-terminal HSDH domain found in bacteria (Escherichia coli (EC) ThrA) and higher plants (Zea mays AK-HSDH). AK and HSDH are the first and third enzymes in the biosynthetic pathway of the aspartate family of amino acids. AK catalyzes the phosphorylation of Asp to P-aspartyl phosphate. HSDH catalyzes the NADPH-dependent conversion of Asp 3-semialdehyde to homoserine. HSDH is the first committed reaction in the branch of the pathway that leads to Thr and Met. In E. coli, ThrA is subject to allosteric regulation by the end product L-threonine and the native enzyme is reported to be tetrameric. As with bacteria, plant AK and HSDH are feedback inhibited by pathway end products. Maize AK-HSDH is a Thr-sensitive 180-kD enzyme. Arabidopsis AK-HSDH is an alanine-activated, threonine-sensitive enzyme whose ACT domains were shown to be involved in allosteric activation. Also included in this CD is the first of two ACT domains of a tetrameric, monofunctional, threonine-sensitive, AK found in Methanococcus jannaschii and other related archaeal species. Members of this CD belong to the superfamily of ACT regulatory domains.

Pssm-ID: 153193 [Multi-domain] Cd Length: 80 Bit Score: 48.36 E-value: 4.18e-08

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 705441832  38 RGVPNEPGMAAKVFTQLAEAGVNVDMIVQAGASTGtadISFTVPETTVRSVQEVLE 93
Cdd:cd04921    9 TGMVGVPGIAARIFSALARAGINVILISQASSEHS---ISFVVDESDADKALEALE 61

aspartokinase

Pssm-ID: 178166 [Multi-domain] Cd Length: 521 Bit Score: 49.73 E-value: 2.51e-07

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 705441832  45 GMAAKVFTQLAEAGVNVDMIvqagaSTGTADISFTVPETTVRS---VQEVLEVKQDELGYQAFEINNNVGKVAVVGVGMK 121
Cdd:PLN02551 381 GFLAKVFSTFEDLGISVDVV-----ATSEVSISLTLDPSKLWSrelIQQELDHLVEELEKIAVVNLLQGRSIISLIGNVQ 455

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|..
gi 705441832 122 THSGVAAKFFNALSEHGINVLMIS--TSEIRIAALVPLPELDDAVRALHTAY 171
Cdd:PLN02551 456 RSSLILEKVFRVLRTNGVNVQMISqgASKVNISLIVNDDEAEQCVRALHSAF 507

ACT domains of the bifunctional enzyme aspartokinase (AK) - homoserine dehydrogenase (HSDH); This CD includes the second of two ACT domains of the bifunctional enzyme aspartokinase (AK) - homoserine dehydrogenase (HSDH). The ACT domains are positioned between the N-terminal catalytic domain of AK and the C-terminal HSDH domain found in bacteria (Escherichia coli (EC) ThrA) and higher plants (Zea mays AK-HSDH). AK and HSDH are the first and third enzymes in the biosynthetic pathway of the aspartate family of amino acids. AK catalyzes the phosphorylation of Asp to P-aspartyl phosphate. HSDH catalyzes the NADPH-dependent conversion of Asp 3-semialdehyde to homoserine. HSDH is the first committed reaction in the branch of the pathway that leads to Thr and Met. In E. coli, ThrA is subject to allosteric regulation by the end product L-threonine and the native enzyme is reported to be tetrameric. As with bacteria, plant AK and HSDH are feedback inhibited by pathway end products. Maize AK-HSDH is a Thr-sensitive 180-kD enzyme. Arabidopsis AK-HSDH is an alanine-activated, threonine-sensitive enzyme whose ACT domains were shown to be involved in allosteric activation. Members of this CD belong to the superfamily of ACT regulatory domains.

Pssm-ID: 153194 [Multi-domain] Cd Length: 66 Bit Score: 45.42 E-value: 4.10e-07

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|.
gi 705441832 120 MKTHSGVAAKFFNALSEHGINVLMIS--TSEIRIAALVPLPELDDAVRALH 168
Cdd:cd04922   11 MAGTPGVAATFFSALAKANVNIRAIAqgSSERNISAVIDEDDATKALRAVH 61

ACT domain; This family of domains generally have a regulatory role. ACT domains are linked to a wide range of metabolic enzymes that are regulated by amino acid concentration. Pairs of ACT domains bind specifically to a particular amino acid leading to regulation of the linked enzyme. The ACT domain is found in: D-3-phosphoglycerate dehydrogenase EC:1.1.1.95, which is inhibited by serine. Aspartokinase EC:2.7.2.4, which is regulated by lysine. Acetolactate synthase small regulatory subunit, which is inhibited by valine. Phenylalanine-4-hydroxylase EC:1.14.16.1, which is regulated by phenylalanine. Prephenate dehydrogenase EC:4.2.1.51. formyltetrahydrofolate deformylase EC:3.5.1.10, which is activated by methionine and inhibited by glycine. GTP pyrophosphokinase EC:2.7.6.5

Pssm-ID: 426468 [Multi-domain] Cd Length: 66 Bit Score: 44.99 E-value: 5.76e-07

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 705441832   39 GVPNEPGMAAKVFTQLAEAGVNVDMIVQaGASTGTADISFTVPETTVRSVQEVLE 93
Cdd:pfam01842   6 LVPDRPGLLARVLGALADRGINITSIEQ-GTSEDKGGIVFVVIVVDEEDLEEVLE 59

aspartate kinase; Reviewed

Pssm-ID: 236364 [Multi-domain] Cd Length: 454 Bit Score: 46.33 E-value: 3.14e-06

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....
gi 705441832 120 MKTHSGVAAKFFNALSEHGINVLMIS--TSEIRIAALVPLPELDDAVRALHTAY 171
Cdd:PRK09034 395 MRQTVGVAAKITKALAEANINIQMINqgSSEISIMFGVKNEDAEKAVKAIYNAF 448

ACT domains of a monofunctional aspartokinase found mostly in Archaea species (ACT_AK-Arch_2); Included in this CD is the second of two ACT domains of a monofunctional aspartokinase found mostly in Archaea species (ACT_AK-Arch_2). The first or N-terminal ACT domain of these proteins cluster with the ThrA-like ACT 1 domains (ACT_AKi-HSDH-ThrA-like_1) which includes the threonine-sensitive archaeal Methanococcus jannaschii aspartokinase ACT 1 domain. Members of this CD belong to the superfamily of ACT regulatory domains.

Pssm-ID: 153196 [Multi-domain] Cd Length: 66 Bit Score: 42.88 E-value: 3.75e-06

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 705441832 116 VGVGMKTHSGVAAKFFNALSEHGINVLMIS--TSEIRIAALVPLPELDDAVRALHTAYGL 173
Cdd:cd04924    7 VGSGMRGTPGVAGRVFGALGKAGINVIMISqgSSEYNISFVVAEDDGWAAVKAVHDEFGL 66

ACT domains are commonly involved in specifically binding an amino acid or other small ligand leading to regulation of the enzyme; Members of this CD belong to the superfamily of ACT regulatory domains. Pairs of ACT domains are commonly involved in specifically binding an amino acid or other small ligand leading to regulation of the enzyme. The ACT domain has been detected in a number of diverse proteins; some of these proteins are involved in amino acid and purine biosynthesis, phenylalanine hydroxylation, regulation of bacterial metabolism and transcription, and many remain to be characterized. ACT domain-containing enzymes involved in amino acid and purine synthesis are in many cases allosteric enzymes with complex regulation enforced by the binding of ligands. The ACT domain is commonly involved in the binding of a small regulatory molecule, such as the amino acids L-Ser and L-Phe in the case of D-3-phosphoglycerate dehydrogenase and the bifunctional chorismate mutase-prephenate dehydratase enzyme (P-protein), respectively. Aspartokinases typically consist of two C-terminal ACT domains in a tandem repeat, but the second ACT domain is inserted within the first, resulting in, what is normally the terminal beta strand of ACT2, formed from a region N-terminal of ACT1. ACT domain repeats have been shown to have nonequivalent ligand-binding sites with complex regulatory patterns such as those seen in the bifunctional enzyme, aspartokinase-homoserine dehydrogenase (ThrA). In other enzymes, such as phenylalanine hydroxylases, the ACT domain appears to function as a flexible small module providing allosteric regulation via transmission of conformational changes, these conformational changes are not necessarily initiated by regulatory ligand binding at the ACT domain itself. ACT domains are present either singularly, N- or C-terminal, or in pairs present C-terminal or between two catalytic domains. Unique to cyanobacteria are four ACT domains C-terminal to an aspartokinase domain. A few proteins are composed almost entirely of ACT domain repeats as seen in the four ACT domain protein, the ACR protein, found in higher plants; and the two ACT domain protein, the glycine cleavage system transcriptional repressor (GcvR) protein, found in some bacteria. Also seen are single ACT domain proteins similar to the Streptococcus pneumoniae ACT domain protein (uncharacterized pdb structure 1ZPV) found in both bacteria and archaea. Purportedly, the ACT domain is an evolutionarily mobile ligand binding regulatory module that has been fused to different enzymes at various times.

Pssm-ID: 153139 [Multi-domain] Cd Length: 60 Bit Score: 40.74 E-value: 1.92e-05

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 705441832  40 VPNEPGMAAKVFTQLAEAGVNVDMIVQA-GASTGTADISFTVPETTVRS-VQEVLE 93
Cdd:cd02116    5 GPDRPGLLAKVLSVLAEAGINITSIEQRtSGDGGEADIFIVVDGDGDLEkLLEALE 60

ACT domains located C-terminal to the catalytic domain of the lysine plus threonine-sensitive aspartokinase isoenzyme AKIII; This CD includes the second of two ACT domains located C-terminal to the catalytic domain of the lysine plus threonine-sensitive aspartokinase isoenzyme AKIII, a monofunctional class enzyme found in Bacilli (Bacillus subtilis (BS) YclM) and Clostridia species. Aspartokinase is the first enzyme in the aspartate metabolic pathway and catalyzes the conversion of aspartate and ATP to aspartylphosphate and ADP. B. subtilis YclM is reported to be a single polypeptide of 50 kD. AKIII from B. subtilis strain 168 is induced by lysine and repressed by threonine and it is synergistically inhibited by lysine and threonine. Members of this CD belong to the superfamily of ACT regulatory domains.

Pssm-ID: 153188 [Multi-domain] Cd Length: 66 Bit Score: 40.70 E-value: 2.02e-05

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....
gi 705441832 120 MKTHSGVAAKFFNALSEHGINVLMIS--TSEIRIAALVPLPELDDAVRALHTAY 171
Cdd:cd04916   11 MKNTVGVSARATAALAKAGINIRMINqgSSEISIMIGVHNEDADKAVKAIYEEF 64

ACT domains C-terminal to the catalytic domain of aspartokinase (AK; 4-L-aspartate-4-phosphotransferase); This CD includes the second of two ACT domains C-terminal to the catalytic domain of aspartokinase (AK; 4-L-aspartate-4-phosphotransferase). The exception in this group, is the inclusion of the first ACT domain of the bifunctional aspartokinase - homoserine dehydrogenase-like enzyme group (ACT_AKi-HSDH-ThrA-like_1) which includes the monofunctional, threonine-sensitive, aspartokinase found in Methanococcus jannaschii and other related archaeal species. AK catalyzes the conversion of aspartate and ATP to aspartylphosphate and ADP. AK is the first enzyme in the pathway of the biosynthesis of the aspartate family of amino acids (lysine, threonine, methionine, and isoleucine) and the bacterial cell wall component, meso-diaminopimelate. One mechanism for the regulation of this pathway is by the production of several isoenzymes of AK with different repressors and allosteric inhibitors. Pairs of ACT domains are proposed to specifically bind amino acids leading to allosteric regulation of the enzyme. In Escherichia coli (EC), three different AK isoenzymes are regulated specifically by lysine, methionine, and threonine. AK-HSDHI (ThrA) and AK-HSDHII (MetL) are bifunctional enzymes that consist of an N-terminal AK and a C-terminal homoserine dehydrogenase (HSDH). ThrA and MetL are involved in threonine and methionine biosynthesis, respectively. The third isoenzyme, AKIII (LysC), is monofunctional and is involved in lysine synthesis. The three Bacillus subtilis (BS) isoenzymes, AKI (DapG), AKII (LysC), and AKIII (YclM), are feedback inhibited by meso-diaminopimelate, lysine, and lysine plus threonine, respectively. The E. coli lysine-sensitive AK is described as a homodimer, whereas, the B. subtilis lysine-sensitive AK is described as is a heterodimeric complex of alpha- and beta- subunits that are formed from two in-frame overlapping genes. A single AK enzyme type has been described in Pseudomonas, Amycolatopsis, and Corynebacterium, and apparently, unique to cyanobacteria, are AKs with two tandem pairs of ACT domains, C-terminal to the catalytic domain. The fungal aspartate pathway is regulated at the AK step, with L-Thr being an allosteric inhibitor of the Saccharomyces cerevisiae AK (Hom3). At least two distinct AK isoenzymes can occur in higher plants, a monofunctional lysine-sensitive isoenzyme, which is involved in the overall regulation of the pathway and can be synergistically inhibited by S-adenosylmethionine. The other isoenzyme is a bifunctional, threonine-sensitive AK-HSDH protein. Also included in this CD are the ACT domains of the Methylomicrobium alcaliphilum AK; the first enzyme of the ectoine biosynthetic pathway found in this bacterium and several other halophilic/halotolerant bacteria. Members of this CD belong to the superfamily of ACT regulatory domains.

Pssm-ID: 153164 [Multi-domain] Cd Length: 65 Bit Score: 40.56 E-value: 2.84e-05

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*
gi 705441832  38 RGVPNEPGMAAKVFTQLAEAGVNVDMIVQaGAStgTADISFTVPE 82
Cdd:cd04892    8 AGMRGTPGVAARIFSALAEAGINIIMISQ-GSS--EVNISFVVDE 49

bifunctional aspartokinase I/homoserine dehydrogenase I; Provisional

Pssm-ID: 181856 [Multi-domain] Cd Length: 819 Bit Score: 43.22 E-value: 3.74e-05

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 705441832 120 MKTHSGVAAKFFNALSEHGINVLMI--STSEIRIAALVPLPELDDAVRALHTAYG--LDADRIEAV 181
Cdd:PRK09436 325 MKGMVGMASRVFAALSRAGISVVLItqSSSEYSISFCVPQSDAAKAKRALEEEFAleLKEGLLEPL 390

ACT domains of the lysine-sensitive, aspartokinase (AK) isoenzyme AKII of Bacillus subtilis (BS) strain 168 and related domains; This CD includes the C-terminal of the two ACT domains of the lysine-sensitive, aspartokinase (AK) isoenzyme AKII of Bacillus subtilis (BS) strain 168, and the lysine plus threonine-sensitive aspartokinase of Corynebacterium glutamicum, and related sequences. In B. subtilis strain 168, the regulation of the diaminopimelate (Dap)-lysine biosynthetic pathway involves dual control by Dap and lysine, effected through separate Dap- and lysine-sensitive AK isoenzymes. The B. subtilis strain 168 AKII is induced by methionine and repressed and inhibited by lysine. Although C. glutamicum is known to contain a single AK, both the succinylase and dehydrogenase variant pathways of DAP-lysine synthesis operate simultaneously in this organism. In corynebacteria and other various Gram-positive bacteria, the DAP-lysine pathway is feedback regulated by the concerted action of lysine and threonine. Conserved residues in the ACT domains have been shown to be involved in this concerted feedback inhibition. Also included in this CD are the AKs of the extreme thermophile, Thermus thermophilus HB27, the Gram-negative obligate methylotroph, Methylophilus methylotrophus AS1, and those single AKs found in Pseudomons, C. glutamicum, and Amycolatopsis lactamdurans. B. subtilis strain 168 AKII, and the C. glutamicum, Streptomyces clavuligerus and A. lactamdurans AKs are described as tetramers consisting of two alpha and two beta subunits; the alpha (44 kD) and beta (18 kD) subunits formed by two in-phase overlapping polypeptides. This CD includes the second ACT domain C-terminal to the AK catalytic domain of the alpha subunit and the second ACT domain of the beta subunit that lacks the AK catalytic domain. Unlike the C. glutamicum AK beta subunit, which is involved in feedback regulation, the B. subtilis AKII beta subunit is not. Cyanobacteria AKs are unique to this CD and they have a unique domain architecture with two tandem pairs of ACT domains, C-terminal to the catalytic AK domain. In this CD, the second and fourth cyanobacteria AK ACT domains are present. Members of this CD belong to the superfamily of ACT regulatory domains.

Pssm-ID: 153208 Cd Length: 63 Bit Score: 39.44 E-value: 5.57e-05

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....
gi 705441832  39 GVPNEPGMAAKVFTQLAEAGVNVDMIvqagaSTGTADISFTVPE 82
Cdd:cd04936    9 GMRSHPGVAAKMFEALAEAGINIEMI-----STSEIKISCLIDE 47

ACT domains of the lysine-sensitive aspartokinase isoenzyme AKII of Bacillus subtilis (BS) strain 168 and related domains; This CD includes the C-terminal of the two ACT domains of the lysine-sensitive aspartokinase isoenzyme AKII of Bacillus subtilis (BS) strain 168, and the lysine plus threonine-sensitive aspartokinase of Corynebacterium glutamicum, as well as, the second and fourth, of four, ACT domains present in cyanobacteria AK. Also included are the C-terminal of the two ACT domains of the diaminopimelate-sensitive aspartokinase isoenzyme AKI found in Bacilli (B. subtilis strain 168), Clostridia, and Actinobacteria bacterial species. Members of this CD belong to the superfamily of ACT regulatory domains.

Pssm-ID: 153195 Cd Length: 63 Bit Score: 39.04 E-value: 7.47e-05

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....
gi 705441832  39 GVPNEPGMAAKVFTQLAEAGVNVDMIvqagaSTGTADISFTVPE 82
Cdd:cd04923    9 GMRSHPGVAAKMFKALAEAGINIEMI-----STSEIKISCLVDE 47

ACT domains of the diaminopimelate-sensitive aspartokinase (AK) isoenzyme AKI; This CD includes the C-terminal of the two ACT domains of the diaminopimelate-sensitive aspartokinase (AK) isoenzyme AKI, a monofunctional class enzyme found in Bacilli (Bacillus subtilis (BS) strain 168), Clostridia, and Actinobacteria bacterial species. In B. subtilis, the regulation of the diaminopimelate-lysine biosynthetic pathway involves dual control by diaminopimelate and lysine, effected through separate diaminopimelate- and lysine-sensitive AK isoenzymes. AKI activity is invariant during the exponential and stationary phases of growth and is not altered by addition of amino acids to the growth medium. The role of this isoenzyme is most likely to provide a constant level of aspartyl-beta-phosphate for the biosynthesis of diaminopimelate for peptidoglycan synthesis and dipicolinate during sporulation. The BS AKI is tetrameric consisting of two alpha and two beta subunits; the alpha (43 kD) and beta (17 kD) subunit formed by two in-phase overlapping genes. The alpha subunit contains the AK catalytic domain and two ACT domains. The beta subunit contains two ACT domains. Members of this CD belong to the superfamily of ACT regulatory domains.

Pssm-ID: 153209 Cd Length: 64 Bit Score: 38.91 E-value: 1.07e-04

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|
gi 705441832 124 SGVAAKFFNALSEHGINVLMISTSEIRIAALVPLPELDDAVRALHTAYGL 173
Cdd:cd04937   15 PGVMAKIVGALSKEGIEILQTADSHTTISCLVSEDDVKEAVNALHEAFEL 64

ACT domains located C-terminal to the catalytic domain of the aspartokinase (AK) HOM3; This CD includes the second of two ACT domains located C-terminal to the catalytic domain of the aspartokinase (AK) HOM3, a monofunctional class enzyme found in Saccharomyces cerevisiae, and other related ACT domains. AK is the first enzyme in the aspartate metabolic pathway, catalyzes the conversion of aspartate and ATP to aspartylphosphate and ADP, and in fungi, is responsible for the production of threonine, isoleucine and methionine. S. cerevisiae has a single AK, which is regulated by feedback, allosteric inhibition by L-threonine. Recent studies shown that the allosteric transition triggered by binding of threonine to AK involves a large change in the conformation of the native hexameric enzyme that is converted to an inactive one of different shape and substantially smaller hydrodynamic size. Members of this CD belong to the superfamily of ACT regulatory domains.

Pssm-ID: 153191 Cd Length: 66 Bit Score: 38.27 E-value: 1.55e-04

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|.
gi 705441832 120 MKTHSGVAAKFFNALSEHGINVLMIS--TSEIRIAALVplpELDDAVRALH 168
Cdd:cd04919   11 MKNMIGIAGRMFTTLADHRINIEMISqgASEINISCVI---DEKDAVKALN 58

homoserine dehydrogenase; Provisional

Pssm-ID: 235783 [Multi-domain] Cd Length: 426 Bit Score: 40.44 E-value: 3.31e-04

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....
gi 705441832  40 VPNEPGMAAKVFTQLAEAGVNVDMIVQAGASTGTADISFTVPETTVRSVQEVLE 93
Cdd:PRK06349 355 VADKPGVLAKIAAIFAENGISIESILQKGAGGEGAEIVIVTHETSEAALRAALA 408

ACT domains are commonly involved in specifically binding an amino acid or other small ligand leading to regulation of the enzyme; Members of this CD belong to the superfamily of ACT regulatory domains. Pairs of ACT domains are commonly involved in specifically binding an amino acid or other small ligand leading to regulation of the enzyme. The ACT domain has been detected in a number of diverse proteins; some of these proteins are involved in amino acid and purine biosynthesis, phenylalanine hydroxylation, regulation of bacterial metabolism and transcription, and many remain to be characterized. ACT domain-containing enzymes involved in amino acid and purine synthesis are in many cases allosteric enzymes with complex regulation enforced by the binding of ligands. The ACT domain is commonly involved in the binding of a small regulatory molecule, such as the amino acids L-Ser and L-Phe in the case of D-3-phosphoglycerate dehydrogenase and the bifunctional chorismate mutase-prephenate dehydratase enzyme (P-protein), respectively. Aspartokinases typically consist of two C-terminal ACT domains in a tandem repeat, but the second ACT domain is inserted within the first, resulting in, what is normally the terminal beta strand of ACT2, formed from a region N-terminal of ACT1. ACT domain repeats have been shown to have nonequivalent ligand-binding sites with complex regulatory patterns such as those seen in the bifunctional enzyme, aspartokinase-homoserine dehydrogenase (ThrA). In other enzymes, such as phenylalanine hydroxylases, the ACT domain appears to function as a flexible small module providing allosteric regulation via transmission of conformational changes, these conformational changes are not necessarily initiated by regulatory ligand binding at the ACT domain itself. ACT domains are present either singularly, N- or C-terminal, or in pairs present C-terminal or between two catalytic domains. Unique to cyanobacteria are four ACT domains C-terminal to an aspartokinase domain. A few proteins are composed almost entirely of ACT domain repeats as seen in the four ACT domain protein, the ACR protein, found in higher plants; and the two ACT domain protein, the glycine cleavage system transcriptional repressor (GcvR) protein, found in some bacteria. Also seen are single ACT domain proteins similar to the Streptococcus pneumoniae ACT domain protein (uncharacterized pdb structure 1ZPV) found in both bacteria and archaea. Purportedly, the ACT domain is an evolutionarily mobile ligand binding regulatory module that has been fused to different enzymes at various times.

Pssm-ID: 153139 [Multi-domain] Cd Length: 60 Bit Score: 37.27 E-value: 4.06e-04

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|.
gi 705441832 125 GVAAKFFNALSEHGINVLMISTSEIRIAALVPL-------PELDDAVRALH 168
Cdd:cd02116   10 GLLAKVLSVLAEAGINITSIEQRTSGDGGEADIfivvdgdGDLEKLLEALE 60

ACT domains located C-terminal to the catalytic domain of the lysine plus threonine-sensitive aspartokinase isoenzyme AKIII; This CD includes the second of two ACT domains located C-terminal to the catalytic domain of the lysine plus threonine-sensitive aspartokinase isoenzyme AKIII, a monofunctional class enzyme found in Bacilli (Bacillus subtilis (BS) YclM) and Clostridia species. Aspartokinase is the first enzyme in the aspartate metabolic pathway and catalyzes the conversion of aspartate and ATP to aspartylphosphate and ADP. B. subtilis YclM is reported to be a single polypeptide of 50 kD. AKIII from B. subtilis strain 168 is induced by lysine and repressed by threonine and it is synergistically inhibited by lysine and threonine. Members of this CD belong to the superfamily of ACT regulatory domains.

Pssm-ID: 153188 [Multi-domain] Cd Length: 66 Bit Score: 35.69 E-value: 1.33e-03

                         10        20        30
                 ....*....|....*....|....*....|...
gi 705441832  38 RGVPNEPGMAAKVFTQLAEAGVNVDMIVQaGAS 70
Cdd:cd04916    9 EGMKNTVGVSARATAALAKAGINIRMINQ-GSS 40

ACT domains located C-terminal to the catalytic domain of a monofunctional, lysine-sensitive, plant aspartate kinase 1 (AK1); This CD includes the second of two ACT domains located C-terminal to the catalytic domain of a monofunctional, lysine-sensitive, plant aspartate kinase 1 (AK1), which can be synergistically inhibited by S-adenosylmethionine (SAM). This isoenzyme is found in higher plants, Arabidopsis thaliana (AT) and Zea mays, and also in Chlorophyta. In its inactive state, Arabidopsis AK1 binds the effectors lysine and SAM (two molecules each) at the interface of two ACT1 domain subunits. The second ACT domain (ACT2), this CD, does not interact with an effector. Members of this CD belong to the superfamily of ACT regulatory domains.

Pssm-ID: 153190 Cd Length: 65 Bit Score: 35.63 E-value: 1.44e-03

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*
gi 705441832 129 KFFNALSEHGINVLMIS--TSEIRIAALVPLPELDDAVRALHTAY 171
Cdd:cd04918   19 RAFHVLYTKGVNVQMISqgASKVNISLIVNDSEAEGCVQALHKSF 63

ACT domains located C-terminal to the catalytic domain of the lysine-sensitive aspartokinase isoenzyme AKIII; This CD includes the second of two ACT domains located C-terminal to the catalytic domain of the lysine-sensitive aspartokinase isoenzyme AKIII, a monofunctional class enzyme found in bacteria (Escherichia coli (EC) LysC). Aspartokinase is the first enzyme in the aspartate metabolic pathway and catalyzes the conversion of aspartate and ATP to aspartylphosphate and ADP. The E. coli AKIII (LysC) binds two feedback allosteric inhibitor lysine molecules at the dimer interface located between the ACT1 domain of two subunits. The second ACT domain (ACT2), this CD, is not involved in the binding of heterotrophic effectors. Members of this CD belong to the superfamily of ACT regulatory domains.

Pssm-ID: 153189 [Multi-domain] Cd Length: 64 Bit Score: 35.63 E-value: 1.45e-03

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|..
gi 705441832 120 MKTHSGVAAKFFNALSEhgINVLMIS--TSEIRIAALVPLPELDDAVRALHT 169
Cdd:cd04917   11 ISETAGVEKRIFDALED--INVRMICygASNHNLCFLVKEEDKDEVVQRLHS 60

ACT domains of a monofunctional aspartokinase found mostly in Archaea species (ACT_AK-Arch_2); Included in this CD is the second of two ACT domains of a monofunctional aspartokinase found mostly in Archaea species (ACT_AK-Arch_2). The first or N-terminal ACT domain of these proteins cluster with the ThrA-like ACT 1 domains (ACT_AKi-HSDH-ThrA-like_1) which includes the threonine-sensitive archaeal Methanococcus jannaschii aspartokinase ACT 1 domain. Members of this CD belong to the superfamily of ACT regulatory domains.

Pssm-ID: 153196 [Multi-domain] Cd Length: 66 Bit Score: 35.17 E-value: 2.26e-03

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....
gi 705441832  39 GVPNEPGMAAKVFTQLAEAGVNVDMIVQaGAStgTADISFTVPE 82
Cdd:cd04924   10 GMRGTPGVAGRVFGALGKAGINVIMISQ-GSS--EYNISFVVAE 50

ACT domain; This family of domains generally have a regulatory role. ACT domains are linked to a wide range of metabolic enzymes that are regulated by amino acid concentration. Pairs of ACT domains bind specifically to a particular amino acid leading to regulation of the linked enzyme. The ACT domain is found in: D-3-phosphoglycerate dehydrogenase EC:1.1.1.95, which is inhibited by serine. Aspartokinase EC:2.7.2.4, which is regulated by lysine. Acetolactate synthase small regulatory subunit, which is inhibited by valine. Phenylalanine-4-hydroxylase EC:1.14.16.1, which is regulated by phenylalanine. Prephenate dehydrogenase EC:4.2.1.51. formyltetrahydrofolate deformylase EC:3.5.1.10, which is activated by methionine and inhibited by glycine. GTP pyrophosphokinase EC:2.7.6.5

Pssm-ID: 426468 [Multi-domain] Cd Length: 66 Bit Score: 34.98 E-value: 2.53e-03

                          10        20        30
                  ....*....|....*....|....*....|....
gi 705441832  120 MKTHSGVAAKFFNALSEHGINVLMISTSEIRIAA 153
Cdd:pfam01842   7 VPDRPGLLARVLGALADRGINITSIEQGTSEDKG 40

ACT_HSDH_Hom CD includes the C-terminal ACT domain of the NAD(P)H-dependent, homoserine dehydrogenase (HSDH) and related domains; The ACT_HSDH_Hom CD includes the C-terminal ACT domain of the NAD(P)H-dependent, homoserine dehydrogenase (HSDH) encoded by the hom gene of Bacillus subtilis and other related sequences. HSDH reduces aspartate semi-aldehyde to the amino acid homoserine, one that is required for the biosynthesis of Met, Thr, and Ile from Asp. Neither the enzyme nor the aspartate pathway is found in the animal kingdom. This mostly bacterial HSDH group has a C-terminal ACT domain and is believed to be involved in enzyme regulation. A C-terminal deletion in the Corynebacterium glutamicum HSDH abolished allosteric inhibition by L-threonine. Members of this CD belong to the superfamily of ACT regulatory domains.

Pssm-ID: 153153 [Multi-domain] Cd Length: 79 Bit Score: 35.18 E-value: 3.36e-03

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 705441832  40 VPNEPGMAAKVFTQLAEAGVNVDMIVQAGAST-GTADISFTVPETTVRSVQEVLE 93
Cdd:cd04881    7 VKDKPGVLAKITGILAEHGISIESVIQKEADGgETAPVVIVTHETSEAALNAALA 61

ACT domains located C-terminal to the catalytic domain of the lysine-sensitive aspartokinase isoenzyme AKIII; This CD includes the first of two ACT domains located C-terminal to the catalytic domain of the lysine-sensitive aspartokinase isoenzyme AKIII, a monofunctional class enzyme found in bacteria (Escherichia coli (EC) LysC) and plants, (Zea mays Ask1, Ask2, and Arabidopsis thaliana AK1). Aspartokinase is the first enzyme in the aspartate metabolic pathway and catalyzes the conversion of aspartate and ATP to aspartylphosphate and ADP. Like the A. thaliana AK1 (AK1-AT), the E. coli AKIII (LysC) has two bound feedback allosteric inhibitor lysine molecules at the dimer interface located between the ACT1 domain of two subunits. The lysine-sensitive plant isoenzyme is synergistically inhibited by S-adenosylmethionine. A homolog of this group appears to be the Saccharomyces cerevisiae AK (Hom3) which clusters with this group as well. Members of this CD belong to the superfamily of ACT regulatory domains.

Pssm-ID: 153184 Cd Length: 75 Bit Score: 34.87 E-value: 3.60e-03

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|.
gi 705441832 124 SGVAAKFFNALSEHGINVLMISTSEIRI-------AALVPLPELDDAVRAL 167
Cdd:cd04912   15 HGFLAKVFEIFAKHGLSVDLISTSEVSVsltldptKNLSDQLLLDALVKDL 65

ACT domains of the lysine-sensitive aspartokinase isoenzyme AKII and related proteins; This CD includes the N-terminal of the two ACT domains of the lysine-sensitive aspartokinase isoenzyme AKII of Bacillus subtilis (BS) strain 168, and the lysine plus threonine-sensitive aspartokinase of Corynebacterium glutamicum, as well as, the first and third, of four, ACT domains present in cyanobacteria AK. Also included are the N-terminal of the two ACT domains of the diaminopimelate-sensitive aspartokinase isoenzyme AKI found in Bacilli (Bacillus subtilis strain 168), Clostridia, and Actinobacteria bacterial species. Members of this CD belong to the superfamily of ACT regulatory domains.

Pssm-ID: 153163 [Multi-domain] Cd Length: 61 Bit Score: 34.45 E-value: 4.04e-03

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*...
gi 705441832 125 GVAAKFFNALSEHGINVLMISTSEIR-----IAALVPLPELDDAVRAL 167
Cdd:cd04891   13 GVAAKIFSALAEAGINVDMIVQSVSRggttdISFTVPKSDLEKALAIL 60

ACT domains of the lysine-sensitive aspartokinase isoenzyme AKII of Bacillus subtilis (BS) strain 168 and related proteins; This CD includes the N-terminal of the two ACT domains of the lysine-sensitive aspartokinase isoenzyme AKII of Bacillus subtilis (BS) strain 168, and the lysine plus threonine-sensitive aspartokinase of Corynebacterium glutamicum, and related sequences. In B. subtilis 168, the regulation of the diaminopimelate (Dap)-lysine biosynthetic pathway involves dual control by Dap and lysine, effected through separate Dap- and lysine-sensitive aspartokinase isoenzymes. The B. subtilis 168 AKII is induced by methionine and repressed and inhibited by lysine. Although Corynebacterium glutamicum is known to contain a single aspartokinase, both the succinylase and dehydrogenase variant pathways of DAP-lysine synthesis operate simultaneously in this organism. In corynebacteria and other various Gram-positive bacteria, the DAP-lysine pathway is feedback regulated by the concerted action of lysine and threonine. Conserved residues in the ACT domains have been shown to be involved in this concerted feedback inhibition. Also included in this CD are the aspartokinases of the extreme thermophile, Thermus thermophilus HB27, the Gram-negative obligate methylotroph, Methylophilus methylotrophus AS1, and those single aspartokinases found in Pseudomonas aeruginosa, C. glutamicum, and Amycolatopsis lactamdurans. B. subtilis 168 AKII, and the C. glutamicum, Streptomyces clavuligerus and A. lactamdurans aspartokinases are described as tetramers consisting of two alpha and two beta subunits; the alpha (44 kD) and beta (18 kD) subunits formed by two in-phase overlapping polypeptides. This CD includes the first ACT domain C-terminal to the AK catalytic domain of the alpha subunit and the first ACT domain of the beta subunit that lacks the AK catalytic domain. Unlike the C. glutamicum AK beta subunit, which is involved in feedback regulation, the B. subtilis AKII beta subunit is not. Cyanobacteria aspartokinases are unique to this CD and they have a unique domain architecture with two tandem pairs of ACT domains, C-terminal to the catalytic AK domain. In this CD, the first and third cyanobacteria AK ACT domains are present. Members of this CD belong to the superfamily of ACT regulatory domains.

Pssm-ID: 153185 Cd Length: 75 Bit Score: 34.04 E-value: 7.00e-03

                         10        20
                 ....*....|....*....|
gi 705441832 125 GVAAKFFNALSEHGINVLMI 144
Cdd:cd04913   14 GVAAKIFGALAEANINVDMI 33