Uncharacterized conserved protein YbjT, contains NAD(P)-binding and DUF2867 domains [General function prediction only];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966986112  21 VFILGASGETGRALLKEILEQGlfSKVTLIGRRKLTFNEEAYKNVNQEVVDFEKLEDYASAFQGHDVGFCCLGttrakAG 100
Cdd:COG0702    2 ILVTGATGFIGRRVVRALLARG--HPVRALVRDPEKAAALAAAGVEVVQGDLDDPESLAAALAGVDAVFLLVP-----SG 74

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 966986112 101 AEGFVRVDRDYVLKSAELAKAGGCKHFNLVSSKGADKSSNFLYLQVKGEVEAKIEELKFDrYSVFRPGV 169
Cdd:COG0702   75 PGGDFAVDVEGARNLADAAKAAGVKRIVYLSALGADRDSPSPYLRAKAAVEEALRASGLP-YTILRPGW 142

Semialdehyde dehydrogenase, NAD binding domain; The semialdehyde dehydrogenase family is found in N-acetyl-glutamine semialdehyde dehydrogenase (AgrC), which is involved in arginine biosynthesis, and aspartate-semialdehyde dehydrogenase, an enzyme involved in the biosynthesis of various amino acids from aspartate. This family is also found in yeast and fungal Arg5,6 protein, which is cleaved into the enzymes N-acety-gamma-glutamyl-phosphate reductase and acetylglutamate kinase. These are also involved in arginine biosynthesis. All proteins in this entry contain a NAD binding region of semialdehyde dehydrogenase.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966986112    20 SVFILGASGETGRALLKEILEQGLFSKVTLIGRR-----KLTFNEEAYKNVNQEVVDFEKLEDYASafqghDVGFCCLGT 94
Cdd:smart00859   1 KVAIVGATGYVGQELLRLLAEHPDFELTALAASSrsagkKVSEAGPHLKGEVVLELDPPDFEELAV-----DIVFLALPH 75

                   ....*...
gi 966986112    95 TRAKAGAE 102
Cdd:smart00859  76 GVSKESAP 83

Extended (e) and atypical (a) SDRs; Extended or atypical short-chain dehydrogenases/reductases (SDRs, aka tyrosine-dependent oxidoreductases) are distinct from classical SDRs. In addition to the Rossmann fold (alpha/beta folding pattern with a central beta-sheet) core region typical of all SDRs, extended SDRs have a less conserved C-terminal extension of approximately 100 amino acids. Extended SDRs are a diverse collection of proteins, and include isomerases, epimerases, oxidoreductases, and lyases; they typically have a TGXXGXXG cofactor binding motif. Atypical SDRs generally lack the catalytic residues characteristic of the SDRs, and their glycine-rich NAD(P)-binding motif is often different from the forms normally seen in classical or extended SDRs. Atypical SDRs include biliverdin IX beta reductase (BVR-B,aka flavin reductase), NMRa (a negative transcriptional regulator of various fungi), progesterone 5-beta-reductase like proteins, phenylcoumaran benzylic ether and pinoresinol-lariciresinol reductases, phenylpropene synthases, eugenol synthase, triphenylmethane reductase, isoflavone reductases, and others. SDRs are a functionally diverse family of oxidoreductases that have a single domain with a structurally conserved Rossmann fold, an NAD(P)(H)-binding region, and a structurally diverse C-terminal region. Sequence identity between different SDR enzymes is typically in the 15-30% range; they catalyze a wide range of activities including the metabolism of steroids, cofactors, carbohydrates, lipids, aromatic compounds, and amino acids, and act in redox sensing. Classical SDRs have an TGXXX[AG]XG cofactor binding motif and a YXXXK active site motif, with the Tyr residue of the active site motif serving as a critical catalytic residue (Tyr-151, human 15-hydroxyprostaglandin dehydrogenase numbering). In addition to the Tyr and Lys, there is often an upstream Ser and/or an Asn, contributing to the active site; while substrate binding is in the C-terminal region, which determines specificity. The standard reaction mechanism is a 4-pro-S hydride transfer and proton relay involving the conserved Tyr and Lys, a water molecule stabilized by Asn, and nicotinamide. Complex (multidomain) SDRs such as ketoreductase domains of fatty acid synthase have a GGXGXXG NAD(P)-binding motif and an altered active site motif (YXXXN). Fungal type ketoacyl reductases have a TGXXXGX(1-2)G NAD(P)-binding motif.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966986112  21 VFILGASGETGRALLKEILEQGlfSKVTLIGRRKLTFNEEAYKNVNQEVVDFEKLEDYASAFQGHDVGFCCLGTTRAKag 100
Cdd:cd05226    1 ILILGATGFIGRALARELLEQG--HEVTLLVRNTKRLSKEDQEPVAVVEGDLRDLDSLSDAVQGVDVVIHLAGAPRDT-- 76

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966986112 101 aEGFVRVDRDYVLKSAELAKAGGCKHFNLVSSKGA--------DKSSNFLYLQVKGEVEAKIEELkFDRYSVFRPGVLLC 172
Cdd:cd05226   77 -RDFCEVDVEGTRNVLEAAKEAGVKHFIFISSLGAygdlheetEPSPSSPYLAVKAKTEAVLREA-SLPYTIVRPGVIYG 154

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*....
gi 966986112 173 DrqesrpgewlvrkffgslpeswasgqsvplvtVVRAMLNNVVRPSDKQ 221
Cdd:cd05226  155 D--------------------------------LARAIANAVVTPGKKN 171

atypical (a) SDRs, subgroup 5; This subgroup contains atypical SDRs, some of which are identified as putative NAD(P)-dependent epimerases, one as a putative NAD-dependent epimerase/dehydratase. Atypical SDRs are distinct from classical SDRs. Members of this subgroup have a glycine-rich NAD(P)-binding motif that is very similar to the extended SDRs, GXXGXXG, and binds NADP. Generally, this subgroup has poor conservation of the active site tetrad; however, individual sequences do contain matches to the YXXXK active site motif, the upstream Ser, and there is a highly conserved Asp in place of the usual active site Asn throughout the subgroup. Atypical SDRs generally lack the catalytic residues characteristic of the SDRs, and their glycine-rich NAD(P)-binding motif is often different from the forms normally seen in classical or extended SDRs. Atypical SDRs include biliverdin IX beta reductase (BVR-B,aka flavin reductase), NMRa (a negative transcriptional regulator of various fungi), progesterone 5-beta-reductase like proteins, phenylcoumaran benzylic ether and pinoresinol-lariciresinol reductases, phenylpropene synthases, eugenol synthase, triphenylmethane reductase, isoflavone reductases, and others. SDRs are a functionally diverse family of oxidoreductases that have a single domain with a structurally conserved Rossmann fold, an NAD(P)(H)-binding region, and a structurally diverse C-terminal region. Sequence identity between different SDR enzymes is typically in the 15-30% range; they catalyze a wide range of activities including the metabolism of steroids, cofactors, carbohydrates, lipids, aromatic compounds, and amino acids, and act in redox sensing. Classical SDRs have an TGXXX[AG]XG cofactor binding motif and a YXXXK active site motif, with the Tyr residue of the active site motif serving as a critical catalytic residue (Tyr-151, human 15-hydroxyprostaglandin dehydrogenase numbering). In addition to the Tyr and Lys, there is often an upstream Ser and/or an Asn, contributing to the active site; while substrate binding is in the C-terminal region, which determines specificity. The standard reaction mechanism is a 4-pro-S hydride transfer and proton relay involving the conserved Tyr and Lys, a water molecule stabilized by Asn, and nicotinamide. In addition to the Rossmann fold core region typical of all SDRs, extended SDRs have a less conserved C-terminal extension of approximately 100 amino acids, and typically have a TGXXGXXG cofactor binding motif. Complex (multidomain) SDRs such as ketoreductase domains of fatty acid synthase have a GGXGXXG NAD(P)-binding motif and an altered active site motif (YXXXN). Fungal type ketoacyl reductases have a TGXXXGX(1-2)G NAD(P)-binding motif.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966986112  21 VFILGASGETGRALLKEILEQGlfSKVTLIGRRKLTFNEEAYKNVNQEVVDFEKLEDYASAFQGHDVGFCCLGTTRAkaG 100
Cdd:cd05243    2 VLVVGATGKVGRHVVRELLDRG--YQVRALVRDPSQAEKLEAAGAEVVVGDLTDAESLAAALEGIDAVISAAGSGGK--G 77

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 966986112 101 AEGFVRVDRDYVLKSAELAKAGGCKHFNLVSSKGADKSSNFL-----YLQVKGEVEAKIEELKFDrYSVFRPGVLL 171
Cdd:cd05243   78 GPRTEAVDYDGNINLIDAAKKAGVKRFVLVSSIGADKPSHPLealgpYLDAKRKAEDYLRASGLD-YTIVRPGGLT 152

triphenylmethane reductase (TMR)-like proteins, NMRa-like, atypical (a) SDRs; TMR is an atypical NADP-binding protein of the SDR family. It lacks the active site residues of the SDRs but has a glycine rich NAD(P)-binding motif that matches the extended SDRs. Proteins in this subgroup however, are more similar in length to the classical SDRs. TMR was identified as a reducer of triphenylmethane dyes, important environmental pollutants. This subgroup also includes Escherichia coli NADPH-dependent quinine oxidoreductase (QOR2), which catalyzes two-electron reduction of quinone; but is unlikely to play a major role in protecting against quinone cytotoxicity. Atypical SDRs are distinct from classical SDRs. Atypical SDRs include biliverdin IX beta reductase (BVR-B,aka flavin reductase), NMRa (a negative transcriptional regulator of various fungi), progesterone 5-beta-reductase like proteins, phenylcoumaran benzylic ether and pinoresinol-lariciresinol reductases, phenylpropene synthases, eugenol synthase, triphenylmethane reductase, isoflavone reductases, and others. SDRs are a functionally diverse family of oxidoreductases that have a single domain with a structurally conserved Rossmann fold, an NAD(P)(H)-binding region, and a structurally diverse C-terminal region. Sequence identity between different SDR enzymes is typically in the 15-30% range; they catalyze a wide range of activities including the metabolism of steroids, cofactors, carbohydrates, lipids, aromatic compounds, and amino acids, and act in redox sensing. Classical SDRs have an TGXXX[AG]XG cofactor binding motif and a YXXXK active site motif, with the Tyr residue of the active site motif serving as a critical catalytic residue (Tyr-151, human 15-hydroxyprostaglandin dehydrogenase numbering). In addition to the Tyr and Lys, there is often an upstream Ser and/or an Asn, contributing to the active site; while substrate binding is in the C-terminal region, which determines specificity. The standard reaction mechanism is a 4-pro-S hydride transfer and proton relay involving the conserved Tyr and Lys, a water molecule stabilized by Asn, and nicotinamide. In addition to the Rossmann fold core region typical of all SDRs, extended SDRs have a less conserved C-terminal extension of approximately 100 amino acids, and typically have a TGXXGXXG cofactor binding motif. Complex (multidomain) SDRs such as ketoreductase domains of fatty acid synthase have a GGXGXXG NAD(P)-binding motif and an altered active site motif (YXXXN). Fungal type ketoacyl reductases have a TGXXXGX(1-2)G NAD(P)-binding motif.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966986112  23 ILGASGETGRALLKEILEQGlfSKVTLIGRRKLTFNEEAYKNVNQEVVDFEKLEDYASAFQGHDVGFCCLGTTRAKAGAE 102
Cdd:cd05269    3 VTGATGKLGTAVVELLLAKV--ASVVALVRNPEKAKAFAADGVEVRQGDYDDPETLERAFEGVDRLLLISPSDLEDRIQQ 80

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 966986112 103 GFVRVDrdyvlksaeLAKAGGCKHFNLVSSKGADKSSNFLYLQVKGEVEAKIEELKFDrYSVFRPG 168
Cdd:cd05269   81 HKNFID---------AAKQAGVKHIVYLSASGADEDSPFLLARDHGATEKYLEASGIP-YTILRPG 136

biliverdin IX beta reductase (BVR-B, aka flavin reductase)-like proteins; atypical (a) SDRs; Human BVR-B catalyzes pyridine nucleotide-dependent production of bilirubin-IX beta during fetal development; in the adult BVR-B has flavin and ferric reductase activities. Human BVR-B catalyzes the reduction of FMN, FAD, and riboflavin. Recognition of flavin occurs mostly by hydrophobic interactions, accounting for the broad substrate specificity. Atypical SDRs are distinct from classical SDRs. BVR-B does not share the key catalytic triad, or conserved tyrosine typical of SDRs. The glycine-rich NADP-binding motif of BVR-B is GXXGXXG, which is similar but not identical to the pattern seen in extended SDRs. Atypical SDRs generally lack the catalytic residues characteristic of the SDRs, and their glycine-rich NAD(P)-binding motif is often different from the forms normally seen in classical or extended SDRs. Atypical SDRs include biliverdin IX beta reductase (BVR-B,aka flavin reductase), NMRa (a negative transcriptional regulator of various fungi), progesterone 5-beta-reductase like proteins, phenylcoumaran benzylic ether and pinoresinol-lariciresinol reductases, phenylpropene synthases, eugenol synthase, triphenylmethane reductase, isoflavone reductases, and others. SDRs are a functionally diverse family of oxidoreductases that have a single domain with a structurally conserved Rossmann fold, an NAD(P)(H)-binding region, and a structurally diverse C-terminal region. Sequence identity between different SDR enzymes is typically in the 15-30% range; they catalyze a wide range of activities including the metabolism of steroids, cofactors, carbohydrates, lipids, aromatic compounds, and amino acids, and act in redox sensing. Classical SDRs have an TGXXX[AG]XG cofactor binding motif and a YXXXK active site motif, with the Tyr residue of the active site motif serving as a critical catalytic residue (Tyr-151, human 15-hydroxyprostaglandin dehydrogenase numbering). In addition to the Tyr and Lys, there is often an upstream Ser and/or an Asn, contributing to the active site; while substrate binding is in the C-terminal region, which determines specificity. The standard reaction mechanism is a 4-pro-S hydride transfer and proton relay involving the conserved Tyr and Lys, a water molecule stabilized by Asn, and nicotinamide. In addition to the Rossmann fold core region typical of all SDRs, extended SDRs have a less conserved C-terminal extension of approximately 100 amino acids, and typically have a TGXXGXXG cofactor binding motif. Complex (multidomain) SDRs such as ketoreductase domains of fatty acid synthase have a GGXGXXG NAD(P)-binding motif and an altered active site motif (YXXXN). Fungal type ketoacyl reductases have a TGXXXGX(1-2)G NAD(P)-binding motif.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966986112  23 ILGASGETGRALLKEILEQGLfsKVTLIGRRKlTFNEEAYKNVNQEVVDFEKLEDYASAFQGHDVGFCCLGTTRAKAGAE 102
Cdd:cd05244    4 IIGATGRTGSAIVREALARGH--EVTALVRDP-AKLPAEHEKLKVVQGDVLDLEDVKEALEGQDAVISALGTRNDLSPTT 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966986112 103 GFVRVDRDYVlksaELAKAGGCKHFNLVSSKG----------ADKSSNFlYLQVKGEVEAKIEELKFDR-----YSVFRP 167
Cdd:cd05244   81 LHSEGTRNIV----SAMKAAGVKRLIVVGGAGslddrpkvtlVLDTLLF-PPALRRVAEDHARMLKVLResgldWTAVRP 155

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|.
gi 966986112 168 GVLLcdrQESRPGEWLVRKF-FGSLPESWASgqsvpLVTVVRAMLNNVVRP 217
Cdd:cd05244  156 PALF---DGGATGGYYRVELlVDAKGGSRIS-----RADLAIFMLDELETP 198

NADH dehydrogenase (ubiquinone) 1 alpha subcomplex, subunit 9, 39 kDa, (NDUFA9) -like, atypical (a) SDRs; This subgroup of extended SDR-like proteins are atypical SDRs. They have a glycine-rich NAD(P)-binding motif similar to the typical SDRs, GXXGXXG, and have the YXXXK active site motif (though not the other residues of the SDR tetrad). Members identified include NDUFA9 (mitochondrial) and putative nucleoside-diphosphate-sugar epimerase. Atypical SDRs generally lack the catalytic residues characteristic of the SDRs, and their glycine-rich NAD(P)-binding motif is often different from the forms normally seen in classical or extended SDRs. Atypical SDRs include biliverdin IX beta reductase (BVR-B,aka flavin reductase), NMRa (a negative transcriptional regulator of various fungi), progesterone 5-beta-reductase like proteins, phenylcoumaran benzylic ether and pinoresinol-lariciresinol reductases, phenylpropene synthases, eugenol synthase, triphenylmethane reductase, isoflavone reductases, and others. SDRs are a functionally diverse family of oxidoreductases that have a single domain with a structurally conserved Rossmann fold, an NAD(P)(H)-binding region, and a structurally diverse C-terminal region. Sequence identity between different SDR enzymes is typically in the 15-30% range; they catalyze a wide range of activities including the metabolism of steroids, cofactors, carbohydrates, lipids, aromatic compounds, and amino acids, and act in redox sensing. Classical SDRs have an TGXXX[AG]XG cofactor binding motif and a YXXXK active site motif, with the Tyr residue of the active site motif serving as a critical catalytic residue (Tyr-151, human 15-hydroxyprostaglandin dehydrogenase numbering). In addition to the Tyr and Lys, there is often an upstream Ser and/or an Asn, contributing to the active site; while substrate binding is in the C-terminal region, which determines specificity. The standard reaction mechanism is a 4-pro-S hydride transfer and proton relay involving the conserved Tyr and Lys, a water molecule stabilized by Asn, and nicotinamide. In addition to the Rossmann fold core region typical of all SDRs, extended SDRs have a less conserved C-terminal extension of approximately 100 amino acids, and typically have a TGXXGXXG cofactor binding motif. Complex (multidomain) SDRs such as ketoreductase domains of fatty acid synthase have a GGXGXXG NAD(P)-binding motif and an altered active site motif (YXXXN). Fungal type ketoacyl reductases have a TGXXXGX(1-2)G NAD(P)-binding motif.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966986112  21 VFILGASGETGRALLKEILEQGlfSKVTLIGRRKLTFNEEAYKNVNQEVV----DFEKLEDYASAFQGHDVGFCCLGTTR 96
Cdd:cd05271    3 VTVFGATGFIGRYVVNRLAKRG--SQVIVPYRCEAYARRLLVMGDLGQVLfvefDLRDDESIRKALEGSDVVINLVGRLY 80

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 966986112  97 AKaGAEGFVRVDRDYVLKSAELAKAGGCKHFNLVSSKGADKSSNFLYLQVKGEVEAKIEELkFDRYSVFRPGV 169
Cdd:cd05271   81 ET-KNFSFEDVHVEGPERLAKAAKEAGVERLIHISALGADANSPSKYLRSKAEGEEAVREA-FPEATIVRPSV 151

NmrA (a transcriptional regulator) and triphenylmethane reductase (TMR) like proteins, subgroup 1, atypical (a) SDRs; Atypical SDRs related to NMRa, TMR, and HSCARG (an NADPH sensor). This subgroup resembles the SDRs and has a partially conserved characteristic [ST]GXXGXXG NAD-binding motif, but lacks the conserved active site residues. NmrA is a negative transcriptional regulator of various fungi, involved in the post-translational modulation of the GATA-type transcription factor AreA. NmrA lacks the canonical GXXGXXG NAD-binding motif and has altered residues at the catalytic triad, including a Met instead of the critical Tyr residue. NmrA may bind nucleotides but appears to lack any dehydrogenase activity. HSCARG has been identified as a putative NADP-sensing molecule, and redistributes and restructures in response to NADPH/NADP ratios. Like NmrA, it lacks most of the active site residues of the SDR family, but has an NAD(P)-binding motif similar to the extended SDR family, GXXGXXG. SDRs are a functionally diverse family of oxidoreductases that have a single domain with a structurally conserved Rossmann fold, an NAD(P)(H)-binding region, and a structurally diverse C-terminal region. Sequence identity between different SDR enzymes is typically in the 15-30% range; they catalyze a wide range of activities including the metabolism of steroids, cofactors, carbohydrates, lipids, aromatic compounds, and amino acids, and act in redox sensing. Atypical SDRs are distinct from classical SDRs. Classical SDRs have an TGXXX[AG]XG cofactor binding motif and a YXXXK active site motif, with the Tyr residue of the active site motif serving as a critical catalytic residue (Tyr-151, human 15-hydroxyprostaglandin dehydrogenase numbering). In addition to the Tyr and Lys, there is often an upstream Ser and/or an Asn, contributing to the active site; while substrate binding is in the C-terminal region, which determines specificity. The standard reaction mechanism is a 4-pro-S hydride transfer and proton relay involving the conserved Tyr and Lys, a water molecule stabilized by Asn, and nicotinamide. In addition to the Rossmann fold core region typical of all SDRs, extended SDRs have a less conserved C-terminal extension of approximately 100 amino acids, and typically have a TGXXGXXG cofactor binding motif. Complex (multidomain) SDRs such as ketoreductase domains of fatty acid synthase have a GGXGXXG NAD(P)-binding motif and an altered active site motif (YXXXN). Fungal type ketoacyl reductases have a TGXXXGX(1-2)G NAD(P)-binding motif.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966986112  23 ILGASGETGRALLKEILEQGlfSKVTLIGRRKLTFNEEAYKNVNQEVVDFEKLEDYASAFQGHDVGFCCL---GTTRAKA 99
Cdd:cd05231    3 VTGATGRIGSKVATTLLEAG--RPVRALVRSDERAAALAARGAEVVVGDLDDPAVLAAALAGVDAVFFLAppaPTADARP 80

                         90       100       110
                 ....*....|....*....|....*....|....*..
gi 966986112 100 GAEGFVRVdrdyvlkSAELAKAGGCKHFNLVSSKGAD 136
Cdd:cd05231   81 GYVQAAEA-------FASALREAGVKRVVNLSSVGAD 110

atypical (a) SDRs, subgroup 6; These atypical SDR family members of unknown function have only a partial match to a prototypical glycine-rich NAD(P)-binding motif consensus, GXXG, which conserves part of the motif of extended SDR. Furthermore, they lack the characteristic active site residues of the SDRs. This subgroup is related to phenylcoumaran benzylic ether reductase, an NADPH-dependent aromatic alcohol reductase. One member is identified as a putative NAD-dependent epimerase/dehydratase. Atypical SDRs generally lack the catalytic residues characteristic of the SDRs, and their glycine-rich NAD(P)-binding motif is often different from the forms normally seen in classical or extended SDRs. Atypical SDRs include biliverdin IX beta reductase (BVR-B,aka flavin reductase), NMRa (a negative transcriptional regulator of various fungi), progesterone 5-beta-reductase like proteins, phenylcoumaran benzylic ether and pinoresinol-lariciresinol reductases, phenylpropene synthases, eugenol synthase, triphenylmethane reductase, isoflavone reductases, and others. SDRs are a functionally diverse family of oxidoreductases that have a single domain with a structurally conserved Rossmann fold, an NAD(P)(H)-binding region, and a structurally diverse C-terminal region. Sequence identity between different SDR enzymes is typically in the 15-30% range; they catalyze a wide range of activities including the metabolism of steroids, cofactors, carbohydrates, lipids, aromatic compounds, and amino acids, and act in redox sensing. Classical SDRs have an TGXXX[AG]XG cofactor binding motif and a YXXXK active site motif, with the Tyr residue of the active site motif serving as a critical catalytic residue (Tyr-151, human 15-hydroxyprostaglandin dehydrogenase numbering). In addition to the Tyr and Lys, there is often an upstream Ser and/or an Asn, contributing to the active site; while substrate binding is in the C-terminal region, which determines specificity. The standard reaction mechanism is a 4-pro-S hydride transfer and proton relay involving the conserved Tyr and Lys, a water molecule stabilized by Asn, and nicotinamide. In addition to the Rossmann fold core region typical of all SDRs, extended SDRs have a less conserved C-terminal extension of approximately 100 amino acids, and typically have a TGXXGXXG cofactor binding motif. Complex (multidomain) SDRs such as ketoreductase domains of fatty acid synthase have a GGXGXXG NAD(P)-binding motif and an altered active site motif (YXXXN). Fungal type ketoacyl reductases have a TGXXXGX(1-2)G NAD(P)-binding motif.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966986112  19 KSVFILGASGETGRALLKEILEQGLFsKVTLIGR---RKLtfneeAYKNVNQEVV--DFEKLEDYASAFQGHDVGFCCLG 93
Cdd:cd05267    1 KKVLILGANGEIAREATTMLLENSNV-ELTLFLRnahRLL-----HLKSARVTVVegDALNSDDLKAAMRGQDVVYANLG 74

                         90
                 ....*....|..
gi 966986112  94 TTRAKAGAEGFV 105
Cdd:cd05267   75 GTDLDQQAENVV 86

3,8-divinyl protochlorophyllide a 8-vinyl reductase

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966986112  12 EDFRMQNKS---VFILGASGETGRALLKEILEQGLfsKVTLIGRRKLTF----NEEAYKNVNQ-------EVVDFEKLED 77
Cdd:PLN02657  51 QSFRSKEPKdvtVLVVGATGYIGKFVVRELVRRGY--NVVAVAREKSGIrgknGKEDTKKELPgaevvfgDVTDADSLRK 128

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966986112  78 YA-SAFQGHDVGFCCLgttrakAGAEGFV----RVDRDYVLKSAELAKAGGCKHFNLVSSKGADKSsnFLYLQ-VKGEVE 151
Cdd:PLN02657 129 VLfSEGDPVDVVVSCL------ASRTGGVkdswKIDYQATKNSLDAGREVGAKHFVLLSAICVQKP--LLEFQrAKLKFE 200

                        170
                 ....*....|....*..
gi 966986112 152 AKIEELKFD-RYSVFRP 167
Cdd:PLN02657 201 AELQALDSDfTYSIVRP 217