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Conserved domains on  [gi|1274095690|ref|NP_001344459|]
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hydroxymethylglutaryl-CoA lyase, mitochondrial isoform 3 [Mus musculus]

Protein Classification

beta/alpha barrel domain-containing protein( domain architecture ID 229392)

beta/alpha barrel domain-containing protein belongs to a large superfamily with a wide variety of enzymatic functions

Graphical summary

 Zoom to residue level

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List of domain hits

 Name Accession Description Interval E-value
TIM super family cl21457
TIM-like beta/alpha barrel domains; A large family of domains similar to triose phosphate ...
 16-256 1.75e-143

TIM-like beta/alpha barrel domains; A large family of domains similar to triose phosphate isomerase (TIM) which, in general, share an eight beta/alpha closed barrel structure.


The actual alignment was detected with superfamily member PLN02746:

Pssm-ID: 473867  Cd Length: 347  Bit Score: 405.71  E-value: 1.75e-143
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1274095690  16 MADHSDVLKGIQKFPGINYPVLTPNMKGFEEAVAAGAKEVSVFGAVSELFTRKNANCSIEESFQRFAGVMQAAQAASISV 95
Cdd:PLN02746   99 LADAKDVMAAVRNLEGARFPVLTPNLKGFEAAIAAGAKEVAVFASASESFSKSNINCSIEESLVRYREVALAAKKHSIPV 178

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1274095690  96 RGYVSCALGCPYEGKVSPAKVAEVAKKLYSMGCYEISLGDTIGVGTPGLMKDMLTAVMHEVPVTALAVHCHDTYGQALAN 175
Cdd:PLN02746  179 RGYVSCVVGCPIEGPVPPSKVAYVAKELYDMGCYEISLGDTIGVGTPGTVVPMLEAVMAVVPVDKLAVHFHDTYGQALAN 258

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1274095690 176 TLVALQMGVSVVDSSVAGLGGCPYAKGASGNLATEDLVYMLNGLGIHTGVNLQKLLEAGDFICQALNRKTSSKVAQATCK 255
Cdd:PLN02746  259 ILVSLQMGISTVDSSVAGLGGCPYAKGASGNVATEDVVYMLNGLGVSTNVDLGKLMAAGDFISKHLGRPSGSKTAVALSA 338


                  .
gi 1274095690 256 L 256
Cdd:PLN02746  339 R 339
 
Name Accession Description Interval E-value
PLN02746 PLN02746
hydroxymethylglutaryl-CoA lyase
 16-256 1.75e-143

hydroxymethylglutaryl-CoA lyase


Pssm-ID: 178347  Cd Length: 347  Bit Score: 405.71  E-value: 1.75e-143
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1274095690  16 MADHSDVLKGIQKFPGINYPVLTPNMKGFEEAVAAGAKEVSVFGAVSELFTRKNANCSIEESFQRFAGVMQAAQAASISV 95
Cdd:PLN02746   99 LADAKDVMAAVRNLEGARFPVLTPNLKGFEAAIAAGAKEVAVFASASESFSKSNINCSIEESLVRYREVALAAKKHSIPV 178

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1274095690  96 RGYVSCALGCPYEGKVSPAKVAEVAKKLYSMGCYEISLGDTIGVGTPGLMKDMLTAVMHEVPVTALAVHCHDTYGQALAN 175
Cdd:PLN02746  179 RGYVSCVVGCPIEGPVPPSKVAYVAKELYDMGCYEISLGDTIGVGTPGTVVPMLEAVMAVVPVDKLAVHFHDTYGQALAN 258

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1274095690 176 TLVALQMGVSVVDSSVAGLGGCPYAKGASGNLATEDLVYMLNGLGIHTGVNLQKLLEAGDFICQALNRKTSSKVAQATCK 255
Cdd:PLN02746  259 ILVSLQMGISTVDSSVAGLGGCPYAKGASGNVATEDVVYMLNGLGVSTNVDLGKLMAAGDFISKHLGRPSGSKTAVALSA 338


                  .
gi 1274095690 256 L 256
Cdd:PLN02746  339 R 339
DRE_TIM_HMGL cd07938
3-hydroxy-3-methylglutaryl-CoA lyase, catalytic TIM barrel domain; ...
 16-239 1.18e-141

3-hydroxy-3-methylglutaryl-CoA lyase, catalytic TIM barrel domain; 3-hydroxy-3-methylglutaryl-CoA lyase (HMGL) catalyzes the cleavage of HMG-CoA to acetyl-CoA and acetoacetate, one of the terminal steps in ketone body generation and leucine degradation, and is a key enzyme in the pathway that supplies metabolic fuel to extrahepatic tissues. Mutations in HMGL cause a human autosomal recessive disorder called primary metabolic aciduria that affects ketogenesis and leucine catabolism and can be fatal due to an inability to tolerate hypoglycemia. HMGL has a TIM barrel domain with a catalytic center containing a divalent cation-binding site formed by a cluster of invariant residues that cap the core of the barrel. The cleavage of HMG-CoA requires the presence of a divalent cation like Mg2+ or Mn2+, and the reaction is thought to involve general acid/base catalysis. This family belongs to the DRE-TIM metallolyase superfamily. DRE-TIM metallolyases include 2-isopropylmalate synthase (IPMS), alpha-isopropylmalate synthase (LeuA), 3-hydroxy-3-methylglutaryl-CoA lyase, homocitrate synthase, citramalate synthase, 4-hydroxy-2-oxovalerate aldolase, re-citrate synthase, transcarboxylase 5S, pyruvate carboxylase, AksA, and FrbC. These members all share a conserved triose-phosphate isomerase (TIM) barrel domain consisting of a core beta(8)-alpha(8) motif with the eight parallel beta strands forming an enclosed barrel surrounded by eight alpha helices. The domain has a catalytic center containing a divalent cation-binding site formed by a cluster of invariant residues that cap the core of the barrel. In addition, the catalytic site includes three invariant residues - an aspartate (D), an arginine (R), and a glutamate (E) - which is the basis for the domain name "DRE-TIM".


Pssm-ID: 163676  Cd Length: 274  Bit Score: 397.92  E-value: 1.18e-141
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1274095690  16 MADHSDVLKGIQKFPGINYPVLTPNMKGFEEAVAAGAKEVSVFGAVSELFTRKNANCSIEESFQRFAGVMQAAQAASISV 95
Cdd:cd07938    51 MADAEEVLAGLPRRPGVRYSALVPNLRGAERALAAGVDEVAVFVSASETFSQKNINCSIAESLERFEPVAELAKAAGLRV 130

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1274095690  96 RGYVSCALGCPYEGKVSPAKVAEVAKKLYSMGCYEISLGDTIGVGTPGLMKDMLTAVMHEVPVTALAVHCHDTYGQALAN 175
Cdd:cd07938   131 RGYVSTAFGCPYEGEVPPERVAEVAERLLDLGCDEISLGDTIGVATPAQVRRLLEAVLERFPDEKLALHFHDTRGQALAN 210

                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1274095690 176 TLVALQMGVSVVDSSVAGLGGCPYAKGASGNLATEDLVYMLNGLGIHTGVNLQKLLEAGDFICQ 239
Cdd:cd07938   211 ILAALEAGVRRFDSSVGGLGGCPFAPGATGNVATEDLVYMLEGMGIETGIDLDKLLAAARWISE 274
HMGL-like pfam00682
HMGL-like; This family contains a diverse set of enzymes. These include various aldolases and ...
 13-237 1.13e-64

HMGL-like; This family contains a diverse set of enzymes. These include various aldolases and a region of pyruvate carboxylase.


Pssm-ID: 459902 [Multi-domain]  Cd Length: 264  Bit Score: 202.57  E-value: 1.13e-64
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1274095690  13 RFLMADHSDVLKGIQKFPGIN--YPVLTPNMKGFEEAVA----AGAKEVSVFGAVSELFTRKNANCSIEESFQRFAGVMQ 86
Cdd:pfam00682  45 PAASEDDFEVVRAIAKVIPHAriLVLCRAREHDIKAAVEalkgAGAVRVHVFIATSDLHRKYKLGKDREEVAKRAVAAVK 124

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1274095690  87 AAQAASISVRgyvscaLGCPYEGKVSPAKVAEVAKKLYSMGCYEISLGDTIGVGTPGLMKDMLTAVMHEVPV-TALAVHC 165
Cdd:pfam00682 125 AARSRGIDVE------FSPEDASRTDPEFLAEVVEAAIEAGATRINIPDTVGVLTPNEAAELISALKARVPNkAIISVHC 198

                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1274095690 166 HDTYGQALANTLVALQMGVSVVDSSVAGLGgcpyakGASGNLATEDLVYMLNGLGIHTGVNLQKLLEAGDFI 237
Cdd:pfam00682 199 HNDLGMAVANSLAAVEAGADRVDGTVNGIG------ERAGNAALEEVAAALEGLGVDTGLDLQRLRSIANLV 264
LeuA COG0119
Isopropylmalate/homocitrate/citramalate synthases [Amino acid transport and metabolism]; ...
 48-244 6.34e-17

Isopropylmalate/homocitrate/citramalate synthases [Amino acid transport and metabolism]; Isopropylmalate/homocitrate/citramalate synthases is part of the Pathway/BioSystem: Isoleucine, leucine, valine biosynthesis


Pssm-ID: 439889 [Multi-domain]  Cd Length: 452  Bit Score: 79.44  E-value: 6.34e-17
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1274095690  48 VAAGAKEVSVFGAVSELFTRKNANCSIEESFQRFAGVMQAAQAASISVRgyVSCalgcpyE--GKVSPAKVAEVAKKLYS 125
Cdd:COG0119    88 KGAGVDRVHLFIKTSDLHVEYKLRKTREEVLEMAVEAVKYAKEHGLEVE--FSA------EdaTRTDPDFLLEVLEAAIE 159

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1274095690 126 MGCYEISLGDTIGVGTPGLMKDMLTAVMHEVPVTALAVHCHDTYGQALANTLVALQMGVSVVDSSVAGLGG-Cpyakgas 204
Cdd:COG0119   160 AGADRINLPDTVGGATPNEVADLIEELRERVPDVILSVHCHNDLGLAVANSLAAVEAGADQVEGTINGIGErA------- 232

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|.
gi 1274095690 205 GNLATEDLV-YMLNGLGIHTGVNLQKLLEAGDFICQALNRK 244
Cdd:COG0119   233 GNAALEEVVmNLKLKYGVDTGIDLSKLTELSRLVSEITGLP 273
 
Name Accession Description Interval E-value
PLN02746 PLN02746
hydroxymethylglutaryl-CoA lyase
 16-256 1.75e-143

hydroxymethylglutaryl-CoA lyase


Pssm-ID: 178347  Cd Length: 347  Bit Score: 405.71  E-value: 1.75e-143
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1274095690  16 MADHSDVLKGIQKFPGINYPVLTPNMKGFEEAVAAGAKEVSVFGAVSELFTRKNANCSIEESFQRFAGVMQAAQAASISV 95
Cdd:PLN02746   99 LADAKDVMAAVRNLEGARFPVLTPNLKGFEAAIAAGAKEVAVFASASESFSKSNINCSIEESLVRYREVALAAKKHSIPV 178

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1274095690  96 RGYVSCALGCPYEGKVSPAKVAEVAKKLYSMGCYEISLGDTIGVGTPGLMKDMLTAVMHEVPVTALAVHCHDTYGQALAN 175
Cdd:PLN02746  179 RGYVSCVVGCPIEGPVPPSKVAYVAKELYDMGCYEISLGDTIGVGTPGTVVPMLEAVMAVVPVDKLAVHFHDTYGQALAN 258

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1274095690 176 TLVALQMGVSVVDSSVAGLGGCPYAKGASGNLATEDLVYMLNGLGIHTGVNLQKLLEAGDFICQALNRKTSSKVAQATCK 255
Cdd:PLN02746  259 ILVSLQMGISTVDSSVAGLGGCPYAKGASGNVATEDVVYMLNGLGVSTNVDLGKLMAAGDFISKHLGRPSGSKTAVALSA 338


                  .
gi 1274095690 256 L 256
Cdd:PLN02746  339 R 339
DRE_TIM_HMGL cd07938
3-hydroxy-3-methylglutaryl-CoA lyase, catalytic TIM barrel domain; ...
 16-239 1.18e-141

3-hydroxy-3-methylglutaryl-CoA lyase, catalytic TIM barrel domain; 3-hydroxy-3-methylglutaryl-CoA lyase (HMGL) catalyzes the cleavage of HMG-CoA to acetyl-CoA and acetoacetate, one of the terminal steps in ketone body generation and leucine degradation, and is a key enzyme in the pathway that supplies metabolic fuel to extrahepatic tissues. Mutations in HMGL cause a human autosomal recessive disorder called primary metabolic aciduria that affects ketogenesis and leucine catabolism and can be fatal due to an inability to tolerate hypoglycemia. HMGL has a TIM barrel domain with a catalytic center containing a divalent cation-binding site formed by a cluster of invariant residues that cap the core of the barrel. The cleavage of HMG-CoA requires the presence of a divalent cation like Mg2+ or Mn2+, and the reaction is thought to involve general acid/base catalysis. This family belongs to the DRE-TIM metallolyase superfamily. DRE-TIM metallolyases include 2-isopropylmalate synthase (IPMS), alpha-isopropylmalate synthase (LeuA), 3-hydroxy-3-methylglutaryl-CoA lyase, homocitrate synthase, citramalate synthase, 4-hydroxy-2-oxovalerate aldolase, re-citrate synthase, transcarboxylase 5S, pyruvate carboxylase, AksA, and FrbC. These members all share a conserved triose-phosphate isomerase (TIM) barrel domain consisting of a core beta(8)-alpha(8) motif with the eight parallel beta strands forming an enclosed barrel surrounded by eight alpha helices. The domain has a catalytic center containing a divalent cation-binding site formed by a cluster of invariant residues that cap the core of the barrel. In addition, the catalytic site includes three invariant residues - an aspartate (D), an arginine (R), and a glutamate (E) - which is the basis for the domain name "DRE-TIM".


Pssm-ID: 163676  Cd Length: 274  Bit Score: 397.92  E-value: 1.18e-141
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1274095690  16 MADHSDVLKGIQKFPGINYPVLTPNMKGFEEAVAAGAKEVSVFGAVSELFTRKNANCSIEESFQRFAGVMQAAQAASISV 95
Cdd:cd07938    51 MADAEEVLAGLPRRPGVRYSALVPNLRGAERALAAGVDEVAVFVSASETFSQKNINCSIAESLERFEPVAELAKAAGLRV 130

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1274095690  96 RGYVSCALGCPYEGKVSPAKVAEVAKKLYSMGCYEISLGDTIGVGTPGLMKDMLTAVMHEVPVTALAVHCHDTYGQALAN 175
Cdd:cd07938   131 RGYVSTAFGCPYEGEVPPERVAEVAERLLDLGCDEISLGDTIGVATPAQVRRLLEAVLERFPDEKLALHFHDTRGQALAN 210

                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1274095690 176 TLVALQMGVSVVDSSVAGLGGCPYAKGASGNLATEDLVYMLNGLGIHTGVNLQKLLEAGDFICQ 239
Cdd:cd07938   211 ILAALEAGVRRFDSSVGGLGGCPFAPGATGNVATEDLVYMLEGMGIETGIDLDKLLAAARWISE 274
PRK05692 PRK05692
hydroxymethylglutaryl-CoA lyase; Provisional
 16-246 1.44e-137

hydroxymethylglutaryl-CoA lyase; Provisional


Pssm-ID: 180206  Cd Length: 287  Bit Score: 388.48  E-value: 1.44e-137
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1274095690  16 MADHSDVLKGIQKFPGINYPVLTPNMKGFEEAVAAGAKEVSVFGAVSELFTRKNANCSIEESFQRFAGVMQAAQAASISV 95
Cdd:PRK05692   57 MADAAEVMAGIQRRPGVTYAALTPNLKGLEAALAAGADEVAVFASASEAFSQKNINCSIAESLERFEPVAEAAKQAGVRV 136

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1274095690  96 RGYVSCALGCPYEGKVSPAKVAEVAKKLYSMGCYEISLGDTIGVGTPGLMKDMLTAVMHEVPVTALAVHCHDTYGQALAN 175
Cdd:PRK05692  137 RGYVSCVLGCPYEGEVPPEAVADVAERLFALGCYEISLGDTIGVGTPGQVRAVLEAVLAEFPAERLAGHFHDTYGQALAN 216

                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1274095690 176 TLVALQMGVSVVDSSVAGLGGCPYAKGASGNLATEDLVYMLNGLGIHTGVNLQKLLEAGDFICQALNRKTS 246
Cdd:PRK05692  217 IYASLEEGITVFDASVGGLGGCPYAPGASGNVATEDVLYMLHGLGIETGIDLDKLVRAGQFIQSKLGRPLP 287
DRE_TIM_metallolyase cd03174
DRE-TIM metallolyase superfamily; The DRE-TIM metallolyase superfamily includes ...
 14-239 2.02e-83

DRE-TIM metallolyase superfamily; The DRE-TIM metallolyase superfamily includes 2-isopropylmalate synthase (IPMS), alpha-isopropylmalate synthase (LeuA), 3-hydroxy-3-methylglutaryl-CoA lyase, homocitrate synthase, citramalate synthase, 4-hydroxy-2-oxovalerate aldolase, re-citrate synthase, transcarboxylase 5S, pyruvate carboxylase, AksA, and FrbC. These members all share a conserved triose-phosphate isomerase (TIM) barrel domain consisting of a core beta(8)-alpha(8) motif with the eight parallel beta strands forming an enclosed barrel surrounded by eight alpha helices. The domain has a catalytic center containing a divalent cation-binding site formed by a cluster of invariant residues that cap the core of the barrel. In addition, the catalytic site includes three invariant residues - an aspartate (D), an arginine (R), and a glutamate (E) - which is the basis for the domain name "DRE-TIM".


Pssm-ID: 163674 [Multi-domain]  Cd Length: 265  Bit Score: 250.07  E-value: 2.02e-83
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1274095690  14 FLMADHSDVLKGIQKF-PGINYPVLTPN-MKGFEEAVAAGAKEVSVFGAVSELFTRKNANCSIEESFQRFAGVMQAAQAA 91
Cdd:cd03174    48 PQMEDDWEVLRAIRKLvPNVKLQALVRNrEKGIERALEAGVDEVRIFDSASETHSRKNLNKSREEDLENAEEAIEAAKEA 127

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1274095690  92 SISVRGYVSCALGCpyegKVSPAKVAEVAKKLYSMGCYEISLGDTIGVGTPGLMKDMLTAVMHEVPVTALAVHCHDTYGQ 171
Cdd:cd03174   128 GLEVEGSLEDAFGC----KTDPEYVLEVAKALEEAGADEISLKDTVGLATPEEVAELVKALREALPDVPLGLHTHNTLGL 203

                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1274095690 172 ALANTLVALQMGVSVVDSSVAGLGgcpyakGASGNLATEDLVYMLNGLGIHTGVNLQKLLEAGDFICQ 239
Cdd:cd03174   204 AVANSLAALEAGADRVDGSVNGLG------ERAGNAATEDLVAALEGLGIDTGIDLEKLLEISRYVEE 265
HMGL-like pfam00682
HMGL-like; This family contains a diverse set of enzymes. These include various aldolases and ...
 13-237 1.13e-64

HMGL-like; This family contains a diverse set of enzymes. These include various aldolases and a region of pyruvate carboxylase.


Pssm-ID: 459902 [Multi-domain]  Cd Length: 264  Bit Score: 202.57  E-value: 1.13e-64
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1274095690  13 RFLMADHSDVLKGIQKFPGIN--YPVLTPNMKGFEEAVA----AGAKEVSVFGAVSELFTRKNANCSIEESFQRFAGVMQ 86
Cdd:pfam00682  45 PAASEDDFEVVRAIAKVIPHAriLVLCRAREHDIKAAVEalkgAGAVRVHVFIATSDLHRKYKLGKDREEVAKRAVAAVK 124

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1274095690  87 AAQAASISVRgyvscaLGCPYEGKVSPAKVAEVAKKLYSMGCYEISLGDTIGVGTPGLMKDMLTAVMHEVPV-TALAVHC 165
Cdd:pfam00682 125 AARSRGIDVE------FSPEDASRTDPEFLAEVVEAAIEAGATRINIPDTVGVLTPNEAAELISALKARVPNkAIISVHC 198

                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1274095690 166 HDTYGQALANTLVALQMGVSVVDSSVAGLGgcpyakGASGNLATEDLVYMLNGLGIHTGVNLQKLLEAGDFI 237
Cdd:pfam00682 199 HNDLGMAVANSLAAVEAGADRVDGTVNGIG------ERAGNAALEEVAAALEGLGVDTGLDLQRLRSIANLV 264
DRE_TIM_HOA cd07943
4-hydroxy-2-oxovalerate aldolase, N-terminal catalytic TIM barrel domain; 4-hydroxy ...
 111-237 3.87e-20

4-hydroxy-2-oxovalerate aldolase, N-terminal catalytic TIM barrel domain; 4-hydroxy 2-ketovalerate aldolase (Also known as 4-hydroxy-2-ketovalerate aldolase and 4-hydroxy-2-oxopentanoate aldolase (HOA)) converts 4-hydroxy-2-oxopentanoate to acetaldehyde and pyruvate, the penultimate step in the meta-cleavage pathway for the degradation of phenols, cresols and catechol. This family includes the Escherichia coli MhpE aldolase, the Pseudomonas DmpG aldolase, and the Burkholderia xenovorans BphI pyruvate aldolase. In Pseudomonas, the DmpG aldolase tightly associates with a dehydrogenase (DmpF ) and is inactive without it. HOA has a canonical TIM-barrel fold with a C-terminal extension that forms a funnel leading to the active site. This family belongs to the DRE-TIM metallolyase superfamily. DRE-TIM metallolyases include 2-isopropylmalate synthase (IPMS), alpha-isopropylmalate synthase (LeuA), 3-hydroxy-3-methylglutaryl-CoA lyase, homocitrate synthase, citramalate synthase, 4-hydroxy-2-oxovalerate aldolase, re-citrate synthase, transcarboxylase 5S, pyruvate carboxylase, AksA, and FrbC. These members all share a conserved triose-phosphate isomerase (TIM) barrel domain consisting of a core beta(8)-alpha(8) motif with the eight parallel beta strands forming an enclosed barrel surrounded by eight alpha helices. The domain has a catalytic center containing a divalent cation-binding site formed by a cluster of invariant residues that cap the core of the barrel. In addition, the catalytic site includes three invariant residues - an aspartate (D), an arginine (R), and a glutamate (E) - which is the basis for the domain name "DRE-TIM".


Pssm-ID: 163681  Cd Length: 263  Bit Score: 86.40  E-value: 3.87e-20
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1274095690 111 VSPAKVAEVAKKLYSMGCYEISLGDTIGVGTPGLMKDMLTAVMHEVPVTALAVHCHDTYGQALANTLVALQMGVSVVDSS 190
Cdd:cd07943   138 ASPEELAEQAKLMESYGADCVYVTDSAGAMLPDDVRERVRALREALDPTPVGFHGHNNLGLAVANSLAAVEAGATRIDGS 217

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*..
gi 1274095690 191 VAGLGGCpyakgaSGNLATEDLVYMLNGLGIHTGVNLQKLLEAGDFI 237
Cdd:cd07943   218 LAGLGAG------AGNTPLEVLVAVLERMGIETGIDLYKLMDAAEDL 258
LeuA COG0119
Isopropylmalate/homocitrate/citramalate synthases [Amino acid transport and metabolism]; ...
 48-244 6.34e-17

Isopropylmalate/homocitrate/citramalate synthases [Amino acid transport and metabolism]; Isopropylmalate/homocitrate/citramalate synthases is part of the Pathway/BioSystem: Isoleucine, leucine, valine biosynthesis


Pssm-ID: 439889 [Multi-domain]  Cd Length: 452  Bit Score: 79.44  E-value: 6.34e-17
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1274095690  48 VAAGAKEVSVFGAVSELFTRKNANCSIEESFQRFAGVMQAAQAASISVRgyVSCalgcpyE--GKVSPAKVAEVAKKLYS 125
Cdd:COG0119    88 KGAGVDRVHLFIKTSDLHVEYKLRKTREEVLEMAVEAVKYAKEHGLEVE--FSA------EdaTRTDPDFLLEVLEAAIE 159

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1274095690 126 MGCYEISLGDTIGVGTPGLMKDMLTAVMHEVPVTALAVHCHDTYGQALANTLVALQMGVSVVDSSVAGLGG-Cpyakgas 204
Cdd:COG0119   160 AGADRINLPDTVGGATPNEVADLIEELRERVPDVILSVHCHNDLGLAVANSLAAVEAGADQVEGTINGIGErA------- 232

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|.
gi 1274095690 205 GNLATEDLV-YMLNGLGIHTGVNLQKLLEAGDFICQALNRK 244
Cdd:COG0119   233 GNAALEEVVmNLKLKYGVDTGIDLSKLTELSRLVSEITGLP 273
PRK08195 PRK08195
4-hyroxy-2-oxovalerate/4-hydroxy-2-oxopentanoic acid aldolase,; Validated
 112-235 1.73e-15

4-hyroxy-2-oxovalerate/4-hydroxy-2-oxopentanoic acid aldolase,; Validated


Pssm-ID: 181282 [Multi-domain]  Cd Length: 337  Bit Score: 74.48  E-value: 1.73e-15
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1274095690 112 SPAKVAEVAKKLYSMGCYEISLGDTIGVGTPGLMKDMLTAVMHEV-PVTALAVHCHDTYGQALANTLVALQMGVSVVDSS 190
Cdd:PRK08195  142 PPEKLAEQAKLMESYGAQCVYVVDSAGALLPEDVRDRVRALRAALkPDTQVGFHGHNNLGLGVANSLAAVEAGATRIDGS 221

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*
gi 1274095690 191 VAGLGGcpyakGAsGNLATEDLVYMLNGLGIHTGVNLQKLLEAGD 235
Cdd:PRK08195  222 LAGLGA-----GA-GNTPLEVLVAVLDRMGWETGVDLYKLMDAAE 260
DRE_TIM_PC_TC_5S cd07937
Pyruvate carboxylase and Transcarboxylase 5S, carboxyltransferase domain; This family includes ...
 117-236 3.68e-15

Pyruvate carboxylase and Transcarboxylase 5S, carboxyltransferase domain; This family includes the carboxyltransferase domains of pyruvate carboxylase (PC) and the transcarboxylase (TC) 5S subunit. Transcarboxylase 5S is a cobalt-dependent metalloenzyme subunit of the biotin-dependent transcarboxylase multienzyme complex. Transcarboxylase 5S transfers carbon dioxide from the 1.3S biotin to pyruvate in the second of two carboxylation reactions catalyzed by TC. The first reaction involves the transfer of carbon dioxide from methylmalonyl-CoA to the 1.3S biotin, and is catalyzed by the 12S subunit. These two steps allow a carboxylate group to be transferred from oxaloacetate to propionyl-CoA to yield pyruvate and methylmalonyl-CoA. The catalytic domain of transcarboxylase 5S has a canonical TIM-barrel fold with a large C-terminal extension that forms a funnel leading to the active site. Transcarboxylase 5S forms a homodimer and there are six dimers per complex. In addition to the catalytic domain, transcarboxylase 5S has several other domains including a carbamoyl-phosphate synthase domain, a biotin carboxylase domain, a carboxyltransferase domain, and an ATP-grasp domain. Pyruvate carboxylase, like TC, is a biotin-dependent enzyme that catalyzes the carboxylation of pyruvate to produce oxaloacetate. In mammals, PC has critical roles in gluconeogenesis, lipogenesis, glyceroneogenesis, and insulin secretion. Inherited PC deficiencies are linked to serious diseases in humans such as lactic acidemia, hypoglycemia, psychomotor retardation, and death. PC is a single-chain enzyme and is active only in its homotetrameric form. PC has three domains, an N-terminal biotin carboxylase domain, a carboxyltransferase domain (this alignment model), and a C-terminal biotin-carboxyl carrier protein domain. This family belongs to the DRE-TIM metallolyase superfamily. DRE-TIM metallolyases include 2-isopropylmalate synthase (IPMS), alpha-isopropylmalate synthase (LeuA), 3-hydroxy-3-methylglutaryl-CoA lyase, homocitrate synthase, citramalate synthase, 4-hydroxy-2-oxovalerate aldolase, re-citrate synthase, transcarboxylase 5S, pyruvate carboxylase, AksA, and FrbC. These members all share a conserved triose-phosphate isomerase (TIM) barrel domain consisting of a core beta(8)-alpha(8) motif with the eight parallel beta strands forming an enclosed barrel surrounded by eight alpha helices. The domain has a catalytic center containing a divalent cation-binding site formed by a cluster of invariant residues that cap the core of the barrel. In addition, the catalytic site includes three invariant residues - an aspartate (D), an arginine (R), and a glutamate (E) - which is the basis for the domain name "DRE-TIM".


Pssm-ID: 163675  Cd Length: 275  Bit Score: 72.85  E-value: 3.68e-15
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1274095690 117 AEVAKKLYSMGCYEISLGDTIGVGTPGLMKDMLTAVMHEVPVtALAVHCHDTYGQALANTLVALQMGVSVVDSSVAGLGG 196
Cdd:cd07937   152 VKLAKELEDMGADSICIKDMAGLLTPYAAYELVKALKKEVGL-PIHLHTHDTSGLAVATYLAAAEAGVDIVDTAISPLSG 230

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|
gi 1274095690 197 cpyakGASGNlATEDLVYMLNGLGIHTGVNLQKLLEAGDF 236
Cdd:cd07937   231 -----GTSQP-STESMVAALRGTGRDTGLDLEKLEEISEY 264
DRE_TIM_IPMS cd07940
2-isopropylmalate synthase (IPMS), N-terminal catalytic TIM barrel domain; 2-isopropylmalate ...
 114-233 6.77e-14

2-isopropylmalate synthase (IPMS), N-terminal catalytic TIM barrel domain; 2-isopropylmalate synthase (IPMS) catalyzes an aldol-type condensation of acetyl-CoA and 2-oxoisovalerate yielding 2-isopropylmalate and CoA, the first committed step in leucine biosynthesis. This family includes the Arabidopsis thaliana IPMS1 and IPMS2 proteins, the Glycine max GmN56 protein, and the Brassica insularis BatIMS protein. This family also includes a group of archeal IPMS-like proteins represented by the Methanocaldococcus jannaschii AksA protein. AksA catalyzes the condensation of alpha-ketoglutarate and acetyl-CoA to form trans-homoaconitate, one of 13 steps in the conversion of alpha-ketoglutarate and acetylCoA to alpha-ketosuberate, a precursor to coenzyme B and biotin. AksA also catalyzes the condensation of alpha-ketoadipate or alpha-ketopimelate with acetylCoA to form, respectively, the (R)-homocitrate homologs (R)-2-hydroxy-1,2,5-pentanetricarboxylic acid and (R)-2-hydroxy-1,2,6- hexanetricarboxylic acid. This family belongs to the DRE-TIM metallolyase superfamily. DRE-TIM metallolyases include 2-isopropylmalate synthase (IPMS), alpha-isopropylmalate synthase (LeuA), 3-hydroxy-3-methylglutaryl-CoA lyase, homocitrate synthase, citramalate synthase, 4-hydroxy-2-oxovalerate aldolase, re-citrate synthase, transcarboxylase 5S, pyruvate carboxylase, AksA, and FrbC. These members all share a conserved triose-phosphate isomerase (TIM) barrel domain consisting of a core beta(8)-alpha(8) motif with the eight parallel beta strands forming an enclosed barrel surrounded by eight alpha helices. The domain has a catalytic center containing a divalent cation-binding site formed by a cluster of invariant residues that cap the core of the barrel. In addition, the catalytic site includes three invariant residues - an aspartate (D), an arginine (R), and a glutamate (E) - which is the basis for the domain name "DRE-TIM".


Pssm-ID: 163678  Cd Length: 268  Bit Score: 69.40  E-value: 6.77e-14
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1274095690 114 AKVAEVAKKLysmGCYEISLGDTIGVGTPGLMKDMLTAVMHEVPVTA--LAVHCHDTYGQALANTLVALQMGVSVVDSSV 191
Cdd:cd07940   146 IEVVEAAIEA---GATTINIPDTVGYLTPEEFGELIKKLKENVPNIKvpISVHCHNDLGLAVANSLAAVEAGARQVECTI 222

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*.
gi 1274095690 192 AGLGgcpyakGASGNLATEDLV----YMLNGLGIHTGVNLQKLLEA 233
Cdd:cd07940   223 NGIG------ERAGNAALEEVVmalkTRYDYYGVETGIDTEELYET 262
DRE_TIM_HOA_like cd07944
4-hydroxy-2-oxovalerate aldolase-like, N-terminal catalytic TIM barrel domain; This family of ...
 110-233 2.26e-13

4-hydroxy-2-oxovalerate aldolase-like, N-terminal catalytic TIM barrel domain; This family of bacterial enzymes is sequence-similar to 4-hydroxy-2-oxovalerate aldolase (HOA) but its exact function is unknown. This family includes the Bacteroides vulgatus Bvu_2661 protein and belongs to the DRE-TIM metallolyase superfamily. DRE-TIM metallolyases include 2-isopropylmalate synthase (IPMS), alpha-isopropylmalate synthase (LeuA), 3-hydroxy-3-methylglutaryl-CoA lyase, homocitrate synthase, citramalate synthase, 4-hydroxy-2-oxovalerate aldolase, re-citrate synthase, transcarboxylase 5S, pyruvate carboxylase, AksA, and FrbC. These members all share a conserved triose-phosphate isomerase (TIM) barrel domain consisting of a core beta(8)-alpha(8) motif with the eight parallel beta strands forming an enclosed barrel surrounded by eight alpha helices. The domain has a catalytic center containing a divalent cation-binding site formed by a cluster of invariant residues that cap the core of the barrel. In addition, the catalytic site includes three invariant residues - an aspartate (D), an arginine (R), and a glutamate (E) - which is the basis for the domain name "DRE-TIM".


Pssm-ID: 163682  Cd Length: 266  Bit Score: 67.97  E-value: 2.26e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1274095690 110 KVSPAKVAEVAKKLYSMGCYEISLGDTIGVGTPGLMKDMLTAVMHEV-PVTALAVHCHDTYGQALANTLVALQMGVSVVD 188
Cdd:cd07944   134 GYSDEELLELLELVNEIKPDVFYIVDSFGSMYPEDIKRIISLLRSNLdKDIKLGFHAHNNLQLALANTLEAIELGVEIID 213

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*
gi 1274095690 189 SSVAGLGgcpyaKGAsGNLATEDLVYMLNGLGIHTgVNLQKLLEA 233
Cdd:cd07944   214 ATVYGMG-----RGA-GNLPTELLLDYLNNKFGKK-YNLEPVLEL 251
aksA PRK11858
trans-homoaconitate synthase; Reviewed
 118-232 3.42e-13

trans-homoaconitate synthase; Reviewed


Pssm-ID: 183341 [Multi-domain]  Cd Length: 378  Bit Score: 68.28  E-value: 3.42e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1274095690 118 EVAKKLYSMGCYEISLGDTIGVGTPGLMKDMLTAVMHEVPVtALAVHCHDTYGQALANTLVALQMGVSVVDSSVAGLGgc 197
Cdd:PRK11858  149 EFAKAAEEAGADRVRFCDTVGILDPFTMYELVKELVEAVDI-PIEVHCHNDFGMATANALAGIEAGAKQVHTTVNGLG-- 225

                          90       100       110
                  ....*....|....*....|....*....|....*.
gi 1274095690 198 pyakGASGNLATEDLVYMLNGL-GIHTGVNLQKLLE 232
Cdd:PRK11858  226 ----ERAGNAALEEVVMALKYLyGIDLGIDTERLYE 257
PRK12331 PRK12331
oxaloacetate decarboxylase subunit alpha;
118-236 6.58e-13

oxaloacetate decarboxylase subunit alpha;


Pssm-ID: 183446 [Multi-domain]  Cd Length: 448  Bit Score: 67.80  E-value: 6.58e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1274095690 118 EVAKKLYSMGCYEISLGDTIGVGTPGLMKDMLTAVMHEVPVtALAVHCHDTYGQALANTLVALQMGVSVVDSSVAglggc 197
Cdd:PRK12331  158 KLAKEMQEMGADSICIKDMAGILTPYVAYELVKRIKEAVTV-PLEVHTHATSGIAEMTYLKAIEAGADIIDTAIS----- 231

                          90       100       110
                  ....*....|....*....|....*....|....*....
gi 1274095690 198 PYAKGASgNLATEDLVYMLNGLGIHTGVNLQKLLEAGDF 236
Cdd:PRK12331  232 PFAGGTS-QPATESMVAALQDLGYDTGLDLEELSEIAEY 269
PRK09282 PRK09282
pyruvate carboxylase subunit B; Validated
 111-244 6.61e-13

pyruvate carboxylase subunit B; Validated


Pssm-ID: 236449 [Multi-domain]  Cd Length: 592  Bit Score: 67.95  E-value: 6.61e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1274095690 111 VSP----AKVAEVAKKLYSMGCYEISLGDTIGVGTPGLMKDMLTAVMHEVPVtALAVHCHDTYGQALANTLVALQMGVSV 186
Cdd:PRK09282  147 TSPvhtiEKYVELAKELEEMGCDSICIKDMAGLLTPYAAYELVKALKEEVDL-PVQLHSHCTSGLAPMTYLKAVEAGVDI 225

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 1274095690 187 VDSSVAglggcPYAKGASgNLATEDLVYMLNGLGIHTGVNLQKLLEAGDfICQALNRK 244
Cdd:PRK09282  226 IDTAIS-----PLAFGTS-QPPTESMVAALKGTPYDTGLDLELLFEIAE-YFREVRKK 276
PRK00915 PRK00915
2-isopropylmalate synthase; Validated
 117-253 1.05e-10

2-isopropylmalate synthase; Validated


Pssm-ID: 234864 [Multi-domain]  Cd Length: 513  Bit Score: 61.28  E-value: 1.05e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1274095690 117 AEVAKKLYSMGCYEISLGDTIGVGTPGLMKDMLTAVMHEVP---VTALAVHCHDTYGQALANTLVALQMGVSVVDSSVAG 193
Cdd:PRK00915  152 CRVVEAAIDAGATTINIPDTVGYTTPEEFGELIKTLRERVPnidKAIISVHCHNDLGLAVANSLAAVEAGARQVECTING 231

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1274095690 194 LGgcpyaKGAsGNLATEDLVYMLN----GLGIHTGVNLQKLLEagdficqalnrkTSSKVAQAT 253
Cdd:PRK00915  232 IG-----ERA-GNAALEEVVMALKtrkdIYGVETGINTEEIYR------------TSRLVSQLT 277
PRK09389 PRK09389
(R)-citramalate synthase; Provisional
 121-245 2.72e-10

(R)-citramalate synthase; Provisional


Pssm-ID: 236493 [Multi-domain]  Cd Length: 488  Bit Score: 59.95  E-value: 2.72e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1274095690 121 KKLYSMGcyeISLG-------DTIGVGTPGLMKDmLTAVMHEVPVTALAVHCHDTYGQALANTLVALQMGVSVVDSSVAG 193
Cdd:PRK09389  146 KELYKAG---IEAGadricfcDTVGILTPEKTYE-LFKRLSELVKGPVSIHCHNDFGLAVANTLAALAAGADQVHVTING 221

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|...
gi 1274095690 194 LGgcpyakGASGNLATEDLVYMLNGL-GIHTGVNLQKLLEagdfICQALNRKT 245
Cdd:PRK09389  222 IG------ERAGNASLEEVVMALKHLyDVETGIKLEELYE----LSRLVSRLT 264
PRK12330 PRK12330
methylmalonyl-CoA carboxytransferase subunit 5S;
112-235 3.20e-10

methylmalonyl-CoA carboxytransferase subunit 5S;


Pssm-ID: 183445 [Multi-domain]  Cd Length: 499  Bit Score: 59.77  E-value: 3.20e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1274095690 112 SPAKVAEVAKKLYSMGCYEISLGDTIGVGTPGLMKDMLTAVMHEV-PVTALAVHCHDTYGQALANTLVALQMGVSVVDSS 190
Cdd:PRK12330  153 TVEGFVEQAKRLLDMGADSICIKDMAALLKPQPAYDIVKGIKEACgEDTRINLHCHSTTGVTLVSLMKAIEAGVDVVDTA 232

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*
gi 1274095690 191 VAGLGGCPyakgasGNLATEDLVYMLNGLGIHTGVNLQKLLEAGD 235
Cdd:PRK12330  233 ISSMSLGP------GHNPTESLVEMLEGTGYTTKLDMDRLLKIRD 271
PRK14040 PRK14040
oxaloacetate decarboxylase subunit alpha;
118-232 5.63e-10

oxaloacetate decarboxylase subunit alpha;


Pssm-ID: 237592 [Multi-domain]  Cd Length: 593  Bit Score: 59.17  E-value: 5.63e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1274095690 118 EVAKKLYSMGCYEISLGDTIGVGTPGLMKDMLTAVMHEVPVTaLAVHCHDTYGQALANTLVALQMGVSVVDSSVAGLgGC 197
Cdd:PRK14040  159 DLAKQLEDMGVDSLCIKDMAGLLKPYAAYELVSRIKKRVDVP-LHLHCHATTGLSTATLLKAIEAGIDGVDTAISSM-SM 236

                          90       100       110
                  ....*....|....*....|....*....|....*
gi 1274095690 198 PYakgasGNLATEDLVYMLNGLGIHTGVNLQKLLE 232
Cdd:PRK14040  237 TY-----GHSATETLVATLEGTERDTGLDILKLEE 266
DRE_TIM_NifV cd07939
Streptomyces rubellomurinus FrbC and related proteins, catalytic TIM barrel domain; FrbC (NifV) ...
 113-252 6.01e-10

Streptomyces rubellomurinus FrbC and related proteins, catalytic TIM barrel domain; FrbC (NifV) of Streptomyces rubellomurinus catalyzes the condensation of acetyl-CoA and alpha-ketoglutarate to form homocitrate and CoA, a reaction similar to one catalyzed by homocitrate synthase. The gene encoding FrbC is one of several genes required for the biosynthesis of FR900098, a potent antimalarial antibiotic. This protein is also required for assembly of the nitrogenase MoFe complex but its exact role is unknown. This family also includes the NifV proteins of Heliobacterium chlorum and Gluconacetobacter diazotrophicus, which appear to be orthologous to FrbC. This family belongs to the DRE-TIM metallolyase superfamily. DRE-TIM metallolyases include 2-isopropylmalate synthase (IPMS), alpha-isopropylmalate synthase (LeuA), 3-hydroxy-3-methylglutaryl-CoA lyase, homocitrate synthase, citramalate synthase, 4-hydroxy-2-oxovalerate aldolase, re-citrate synthase, transcarboxylase 5S, pyruvate carboxylase, AksA, and FrbC. These members all share a conserved triose-phosphate isomerase (TIM) barrel domain consisting of a core beta(8)-alpha(8) motif with the eight parallel beta strands forming an enclosed barrel surrounded by eight alpha helices. The domain has a catalytic center containing a divalent cation-binding site formed by a cluster of invariant residues that cap the core of the barrel. In addition, the catalytic site includes three invariant residues - an aspartate (D), an arginine (R), and a glutamate (E) - which is the basis for the domain name "DRE-TIM".


Pssm-ID: 163677 [Multi-domain]  Cd Length: 259  Bit Score: 57.90  E-value: 6.01e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1274095690 113 PAKVAEVAKKLYSMGCYEISLGDTIGVGTPGLMKDMLTAVMHEVPVtALAVHCHDTYGQALANTLVALQMGVSVVDSSVA 192
Cdd:cd07939   138 PDFLIEFAEVAQEAGADRLRFADTVGILDPFTTYELIRRLRAATDL-PLEFHAHNDLGLATANTLAAVRAGATHVSVTVN 216

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1274095690 193 GLGgcpyakGASGNLATEDLVYMLNGL-GIHTGVNLQKLLEagdfICQalnrktssKVAQA 252
Cdd:cd07939   217 GLG------ERAGNAALEEVVMALKHLyGRDTGIDTTRLPE----LSQ--------LVARA 259
DRE_TIM_HCS cd07948
Saccharomyces cerevisiae homocitrate synthase and related proteins, catalytic TIM barrel ...
 47-195 1.35e-08

Saccharomyces cerevisiae homocitrate synthase and related proteins, catalytic TIM barrel domain; Homocitrate synthase (HCS) catalyzes the condensation of acetyl-CoA and alpha-ketoglutarate to form homocitrate, the first step in the lysine biosynthesis pathway. This family includes the Yarrowia lipolytica LYS1 protein as well as the Saccharomyces cerevisiae LYS20 and LYS21 proteins. This family belongs to the DRE-TIM metallolyase superfamily. DRE-TIM metallolyases include 2-isopropylmalate synthase (IPMS), alpha-isopropylmalate synthase (LeuA), 3-hydroxy-3-methylglutaryl-CoA lyase, homocitrate synthase, citramalate synthase, 4-hydroxy-2-oxovalerate aldolase, re-citrate synthase, transcarboxylase 5S, pyruvate carboxylase, AksA, and FrbC. These members all share a conserved triose-phosphate isomerase (TIM) barrel domain consisting of a core beta(8)-alpha(8) motif with the eight parallel beta strands forming an enclosed barrel surrounded by eight alpha helices. The domain has a catalytic center containing a divalent cation-binding site formed by a cluster of invariant residues that cap the core of the barrel. In addition, the catalytic site includes three invariant residues - an aspartate (D), an arginine (R), and a glutamate (E) - which is the basis for the domain name "DRE-TIM".


Pssm-ID: 163685  Cd Length: 262  Bit Score: 54.26  E-value: 1.35e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1274095690  47 AVAAGAKEVSVFGAVSELFTRKNANCSIEESFQRFAGVMQAAQAASISVRgyVSC--ALGCPYegkvspAKVAEVAKKLY 124
Cdd:cd07948    80 AVETGVDGVDLVFGTSPFLREASHGKSITEIIESAVEVIEFVKSKGIEVR--FSSedSFRSDL------VDLLRVYRAVD 151

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1274095690 125 SMGCYEISLGDTIGVGTPGLMKDMLTAVMHEVPvTALAVHCHDTYGQALANTLVALQMGVSVVDSSVAGLG 195
Cdd:cd07948   152 KLGVNRVGIADTVGIATPRQVYELVRTLRGVVS-CDIEFHGHNDTGCAIANAYAALEAGATHIDTTVLGIG 221
PLN03228 PLN03228
methylthioalkylmalate synthase; Provisional
 55-231 2.68e-08

methylthioalkylmalate synthase; Provisional


Pssm-ID: 178767 [Multi-domain]  Cd Length: 503  Bit Score: 54.16  E-value: 2.68e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1274095690  55 VSVFGAVSELFTRKNANCSIEESFQRFAGVMQAAQAAsisvrGYVSCALGCPYEGKVSPAKVAEVAKKLYSMGCYEISLG 134
Cdd:PLN03228  185 ILAFTSTSDIHMKYKLKKTKEEVIEMAVSSIRYAKSL-----GFHDIQFGCEDGGRSDKEFLCKILGEAIKAGATSVGIA 259

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1274095690 135 DTIGVGTPGLMKDMLTAVMHEVPV---TALAVHCHDTYGQALANTLVALQMGVSVVDSSVAGLGgcpyakGASGNLATED 211
Cdd:PLN03228  260 DTVGINMPHEFGELVTYVKANTPGiddIVFSVHCHNDLGLATANTIAGICAGARQVEVTINGIG------ERSGNASLEE 333

                         170       180
                  ....*....|....*....|....*...
gi 1274095690 212 LV--------YMLNGLgiHTGVNLQKLL 231
Cdd:PLN03228  334 VVmalkcrgaYLMNGV--YTGIDTRQIM 359
DRE_TIM_CMS cd07945
Leptospira interrogans citramalate synthase (CMS) and related proteins, N-terminal catalytic ...
 47-233 4.03e-07

Leptospira interrogans citramalate synthase (CMS) and related proteins, N-terminal catalytic TIM barrel domain; Citramalate synthase (CMS) catalyzes the conversion of pyruvate and acetyl-CoA to (R)-citramalate in the first dedicated step of the citramalate pathway. Citramalate is only found in Leptospira interrogans and a few other microorganisms. This family belongs to the DRE-TIM metallolyase superfamily. DRE-TIM metallolyases include 2-isopropylmalate synthase (IPMS), alpha-isopropylmalate synthase (LeuA), 3-hydroxy-3-methylglutaryl-CoA lyase, homocitrate synthase, citramalate synthase, 4-hydroxy-2-oxovalerate aldolase, re-citrate synthase, transcarboxylase 5S, pyruvate carboxylase, AksA, and FrbC. These members all share a conserved triose-phosphate isomerase (TIM) barrel domain consisting of a core beta(8)-alpha(8) motif with the eight parallel beta strands forming an enclosed barrel surrounded by eight alpha helices. The domain has a catalytic center containing a divalent cation-binding site formed by a cluster of invariant residues that cap the core of the barrel. In addition, the catalytic site includes three invariant residues - an aspartate (D), an arginine (R), and a glutamate (E) - which is the basis for the domain name "DRE-TIM".


Pssm-ID: 163683 [Multi-domain]  Cd Length: 280  Bit Score: 50.07  E-value: 4.03e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1274095690  47 AVAAGAKEVSVFGAVSELFTRKNANCSIEESFQRFAGVMQAAQAASISVRGYV---SCALgcpyegKVSPAKVAEVAKKL 123
Cdd:cd07945    83 IKSAGAKVLNLLTKGSLKHCTEQLRKTPEEHFADIREVIEYAIKNGIEVNIYLedwSNGM------RDSPDYVFQLVDFL 156

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1274095690 124 YSMGCYEISLGDTIGVGTPGLMKDMLTAVMHEVPVTALAVHCHDTYGQALANTLVALQMGVSVVDSSVAGLGgcpyakGA 203
Cdd:cd07945   157 SDLPIKRIMLPDTLGILSPFETYTYISDMVKRYPNLHFDFHAHNDYDLAVANVLAAVKAGIKGLHTTVNGLG------ER 230

                         170       180       190
                  ....*....|....*....|....*....|.
gi 1274095690 204 SGNLATEDLVYMLNG-LGIHTGVNLQKLLEA 233
Cdd:cd07945   231 AGNAPLASVIAVLKDkLKVKTNIDEKRLNRA 261
DRE_TIM_Re_CS cd07947
Clostridium kluyveri Re-citrate synthase and related proteins, catalytic TIM barrel domain; ...
 31-237 9.96e-07

Clostridium kluyveri Re-citrate synthase and related proteins, catalytic TIM barrel domain; Re-citrate synthase (Re-CS) is a Clostridium kluyveri enzyme that converts acetyl-CoA and oxaloacetate to citrate. In most organisms, this reaction is catalyzed by Si-citrate synthase which is Si-face stereospecific with respect to C-2 of oxaloacetate, and phylogenetically unrelated to Re-citrate synthase. Re-citrate synthase is also found in a few other strictly anaerobic organisms. This family belongs to the DRE-TIM metallolyase superfamily. DRE-TIM metallolyases include 2-isopropylmalate synthase (IPMS), alpha-isopropylmalate synthase (LeuA), 3-hydroxy-3-methylglutaryl-CoA lyase, homocitrate synthase, citramalate synthase, 4-hydroxy-2-oxovalerate aldolase, re-citrate synthase, transcarboxylase 5S, pyruvate carboxylase, AksA, and FrbC. These members all share a conserved triose-phosphate isomerase (TIM) barrel domain consisting of a core beta(8)-alpha(8) motif with the eight parallel beta strands forming an enclosed barrel surrounded by eight alpha helices. The domain has a catalytic center containing a divalent cation-binding site formed by a cluster of invariant residues that cap the core of the barrel. In addition, the catalytic site includes three invariant residues - an aspartate (D), an arginine (R), and a glutamate (E) - which is the basis for the domain name "DRE-TIM".


Pssm-ID: 163684  Cd Length: 279  Bit Score: 48.86  E-value: 9.96e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1274095690  31 GINYPVLT----PNMKGFEEAVAAGAKEVSVFGAVSELFTRKNANCSIEESFQRFAGVMQAAQAASISVRgyvsCALG-- 104
Cdd:cd07947    63 GYKFPEVTgwirANKEDLKLVKEMGLKETGILMSVSDYHIFKKLKMTREEAMEKYLEIVEEALDHGIKPR----CHLEdi 138

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1274095690 105 --CPYEGKVSP--AKVAEVAKKlYSMGCYeISLGDTIGVGTP---------------GLMKDMltavmhEVPVTALAVHC 165
Cdd:cd07947   139 trADIYGFVLPfvNKLMKLSKE-SGIPVK-IRLCDTLGYGVPypgaslprsvpkiiyGLRKDC------GVPSENLEWHG 210

                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1274095690 166 HDTYGQALANTLVALQMGVSVVDSSVAGLGgcpyakGASGNLATEDLVYMLNGL-GIHTGVNLQKLLEAGDFI 237
Cdd:cd07947   211 HNDFYKAVANAVAAWLYGASWVNCTLLGIG------ERTGNCPLEAMVIEYAQLkGNFDGMNLEVITEIAEYF 277
DRE_TIM_LeuA3 cd07941
Desulfobacterium autotrophicum LeuA3 and related proteins, N-terminal catalytic TIM barrel ...
 131-195 3.65e-06

Desulfobacterium autotrophicum LeuA3 and related proteins, N-terminal catalytic TIM barrel domain; Desulfobacterium autotrophicum LeuA3 is sequence-similar to alpha-isopropylmalate synthase (LeuA) but its exact function is unknown. Members of this family have an N-terminal TIM barrel domain that belongs to the DRE-TIM metallolyase superfamily. DRE-TIM metallolyases include 2-isopropylmalate synthase (IPMS), alpha-isopropylmalate synthase (LeuA), 3-hydroxy-3-methylglutaryl-CoA lyase, homocitrate synthase, citramalate synthase, 4-hydroxy-2-oxovalerate aldolase, re-citrate synthase, transcarboxylase 5S, pyruvate carboxylase, AksA, and FrbC. These members all share a conserved triose-phosphate isomerase (TIM) barrel domain consisting of a core beta(8)-alpha(8) motif with the eight parallel beta strands forming an enclosed barrel surrounded by eight alpha helices. The domain has a catalytic center containing a divalent cation-binding site formed by a cluster of invariant residues that cap the core of the barrel. In addition, the catalytic site includes three invariant residues - an aspartate (D), an arginine (R), and a glutamate (E) - which is the basis for the domain name "DRE-TIM".


Pssm-ID: 163679  Cd Length: 273  Bit Score: 47.06  E-value: 3.65e-06
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1274095690 131 ISLGDTIGvGT-PGLMKDMLTAVMHEVPVTALAVHCHDTYGQALANTLVALQMGVSVVDSSVAGLG 195
Cdd:cd07941   168 LVLCDTNG-GTlPHEIAEIVKEVRERLPGVPLGIHAHNDSGLAVANSLAAVEAGATQVQGTINGYG 232
PRK14042 PRK14042
pyruvate carboxylase subunit B; Provisional
 118-252 3.69e-06

pyruvate carboxylase subunit B; Provisional


Pssm-ID: 172536 [Multi-domain]  Cd Length: 596  Bit Score: 47.79  E-value: 3.69e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1274095690 118 EVAKKLYSMGCYEISLGDTIGVGTPGLMKDmLTAVMHEVPVTALAVHCHDTYGQALANTLVALQMGVSVVDSSVAGLGGc 197
Cdd:PRK14042  158 ELGKKLAEMGCDSIAIKDMAGLLTPTVTVE-LYAGLKQATGLPVHLHSHSTSGLASICHYEAVLAGCNHIDTAISSFSG- 235

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1274095690 198 pyakGASgNLATEDLVYMLNGLGIHTGVNLQKLLEAGDFIcQALNRKTSSKVAQA 252
Cdd:PRK14042  236 ----GAS-HPPTEALVAALTDTPYDTELDLNILLEIDDYF-KAVRKKYSQFESEA 284
PRK12581 PRK12581
oxaloacetate decarboxylase; Provisional
 119-240 1.40e-05

oxaloacetate decarboxylase; Provisional


Pssm-ID: 79056 [Multi-domain]  Cd Length: 468  Bit Score: 45.88  E-value: 1.40e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1274095690 119 VAKKLYSMGCYEISLGDTIGVGTPGLMKDMLTAV--MHEVPvtaLAVHCHDTYGQALANTLVALQMGVSVVDSSVAglgg 196
Cdd:PRK12581  168 LVKELVEMGADSICIKDMAGILTPKAAKELVSGIkaMTNLP---LIVHTHATSGISQMTYLAAVEAGADRIDTALS---- 240

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....
gi 1274095690 197 cPYAKGASgNLATEDLVYMLNGLGIHTGVNLQKLLEAGDFICQA 240
Cdd:PRK12581  241 -PFSEGTS-QPATESMYLALKEAGYDITLDETLLEQAANHLRQA 282
PRK12999 PRK12999
pyruvate carboxylase; Reviewed
 119-236 3.75e-05

pyruvate carboxylase; Reviewed


Pssm-ID: 237263 [Multi-domain]  Cd Length: 1146  Bit Score: 44.74  E-value: 3.75e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1274095690  119 VAKKLYSMGCYEISLGDTIGVGTPGLMKDMLTAVMHEV--PVtalAVHCHDTYGQALANTLVALQMGVSVVD---SSVAG 193
Cdd:PRK12999   696 LAKELEKAGAHILAIKDMAGLLKPAAAYELVSALKEEVdlPI---HLHTHDTSGNGLATYLAAAEAGVDIVDvavASMSG 772

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|...
gi 1274095690  194 LGGCPyakgasgNLATedLVYMLNGLGIHTGVNLQKLLEAGDF 236
Cdd:PRK12999   773 LTSQP-------SLNS--IVAALEGTERDTGLDLDAIRKLSPY 806
PRK12344 PRK12344
putative alpha-isopropylmalate/homocitrate synthase family transferase; Provisional
 133-195 1.86e-03

putative alpha-isopropylmalate/homocitrate synthase family transferase; Provisional


Pssm-ID: 237068 [Multi-domain]  Cd Length: 524  Bit Score: 39.30  E-value: 1.86e-03
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1274095690 133 LGDTIGvGT-PGLMKDMLTAVMHEVPVtALAVHCHDTYGQALANTLVALQMGVSVVDSSVAGLG 195
Cdd:PRK12344  177 LCDTNG-GTlPHEVAEIVAEVRAAPGV-PLGIHAHNDSGCAVANSLAAVEAGARQVQGTINGYG 238
PycA COG1038
Pyruvate carboxylase [Energy production and conversion]; Pyruvate carboxylase is part of the ...
 163-232 4.10e-03

Pyruvate carboxylase [Energy production and conversion]; Pyruvate carboxylase is part of the Pathway/BioSystem: Urea cycle


Pssm-ID: 440660 [Multi-domain]  Cd Length: 1144  Bit Score: 38.14  E-value: 4.10e-03
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1274095690  163 VHCHDTYGQALANTLVALQMGVSVVD---SSVAGLGGCPyakgasgNLATedLVYMLNGLGIHTGVNLQKLLE 232
Cdd:COG1038    739 LHTHDTSGNQLATYLAAIEAGVDIVDvalASMSGLTSQP-------SLNS--LVAALEGTERDTGLDLDALQE 802
 
Blast search parameters
Data Source: Precalculated data, version = cdd.v.3.21
Preset Options:Database: CDSEARCH/cdd   Low complexity filter: no  Composition Based Adjustment: yes   E-value threshold: 0.01

References:

  • Wang J et al. (2023), "The conserved domain database in 2023", Nucleic Acids Res.51(D)384-8.
  • Lu S et al. (2020), "The conserved domain database in 2020", Nucleic Acids Res.48(D)265-8.
  • Marchler-Bauer A et al. (2017), "CDD/SPARCLE: functional classification of proteins via subfamily domain architectures.", Nucleic Acids Res.45(D)200-3.
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