flavonoid reductase (FR), extended (e) SDRs; This subgroup contains FRs of the extended SDR-type and related proteins. These FRs act in the NADP-dependent reduction of flavonoids, ketone-containing plant secondary metabolites; they have the characteristic active site triad of the SDRs (though not the upstream active site Asn) and a NADP-binding motif that is very similar to the typical extended SDR motif. Extended SDRs 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. 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. 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. 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 4097133   13 VLVTGASGFVGSWLVMKLLQAGYTVRATVRDPANVGKTKPLMDLPGATERLSIWKADLAEEGSFHDAIRGCTGVFHVATP 92
Cdd:cd08958   1 VCVTGASGFIGSWLVKRLLQRGYTVRATVRDPGDEKKVAHLLELEGAKERLKLFKADLLDYGSFDAAIDGCDGVFHVASP 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4097133   93 MDFLSKDPENEVIKPTVEGMISIMRACKEAGTVRRIVFTSSAGTV--NLEERQRPVYDEESWTDVDFCrrvKMTGWMYFV 170
Cdd:cd08958  81 VDFDSEDPEEEMIEPAVKGTLNVLEACAKAKSVKRVVFTSSVAAVvwNPNRGEGKVVDESCWSDLDFC---KKTKLWYAL 157

                ....*
gi 4097133  171 SKTLA 175
Cdd:cd08958 158 SKTLA 162

NAD(P)H-binding;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4097133     17 GASGFVGSWLVMKLLQAGYTVRATVRDPAnvgKTKPLMDLPGATerlsIWKADLAEEGSFHDAIRGCTGVFHVATPMDFL 96
Cdd:pfam13460   1 GATGKIGRLLVKQLLARGHEVTALVRNPE---KLADLEDHPGVE----VVDGDVLDPDDLAEALAGQDAVISALGGGGTD 73

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 4097133     97 SkdpenevikptvEGMISIMRACKEAGtVRRIVFTSSAGTVNLEERQRPVYDEESW 152
Cdd:pfam13460  74 E------------TGAKNIIDAAKAAG-VKRFVLVSSLGVGDEVPGPFGPWNKEML 116

This enzymatic domain is part of bacterial polyketide synthases; It catalyses the first step in the reductive modification of the beta-carbonyl centres in the growing polyketide chain. It uses NADPH to reduce the keto group to a hydroxy group.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4097133      11 GTVLVTGASGFVGS----WLVmkllQAGytVRATV----RDPANVGKTKPLMDLPGATERLSIWKADLAEEGSFHDAIRG 82
Cdd:smart00822   1 GTYLITGGLGGLGRalarWLA----ERG--ARRLVllsrSGPDAPGAAALLAELEAAGARVTVVACDVADRDALAAVLAA 74

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 4097133      83 C-------TGVFHVATPMD---FLSKDPE--NEVIKPTVEGMISIMRACKEAgTVRRIVFTSSAGTV 137
Cdd:smart00822  75 IpavegplTGVIHAAGVLDdgvLASLTPErfAAVLAPKAAGAWNLHELTADL-PLDFFVLFSSIAGV 140

flavonoid reductase (FR), extended (e) SDRs; This subgroup contains FRs of the extended SDR-type and related proteins. These FRs act in the NADP-dependent reduction of flavonoids, ketone-containing plant secondary metabolites; they have the characteristic active site triad of the SDRs (though not the upstream active site Asn) and a NADP-binding motif that is very similar to the typical extended SDR motif. Extended SDRs 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. 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. 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. 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 4097133   13 VLVTGASGFVGSWLVMKLLQAGYTVRATVRDPANVGKTKPLMDLPGATERLSIWKADLAEEGSFHDAIRGCTGVFHVATP 92
Cdd:cd08958   1 VCVTGASGFIGSWLVKRLLQRGYTVRATVRDPGDEKKVAHLLELEGAKERLKLFKADLLDYGSFDAAIDGCDGVFHVASP 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4097133   93 MDFLSKDPENEVIKPTVEGMISIMRACKEAGTVRRIVFTSSAGTV--NLEERQRPVYDEESWTDVDFCrrvKMTGWMYFV 170
Cdd:cd08958  81 VDFDSEDPEEEMIEPAVKGTLNVLEACAKAKSVKRVVFTSSVAAVvwNPNRGEGKVVDESCWSDLDFC---KKTKLWYAL 157

                ....*
gi 4097133  171 SKTLA 175
Cdd:cd08958 158 SKTLA 162

cinnamyl-alcohol dehydrogenase family protein

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4097133     9 EKGTVLVTGASGFVGSWLVMKLLQAGYTVRATVRDPANVGKTKPLMDLPGATERLSIWKADLAEEGSFHDAIRGCTGVFH 88
Cdd:PLN02662   3 EGKVVCVTGASGYIASWLVKLLLQRGYTVKATVRDPNDPKKTEHLLALDGAKERLHLFKANLLEEGSFDSVVDGCEGVFH 82

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4097133    89 VATPMDFLSKDPENEVIKPTVEGMISIMRACKEAGTVRRIVFTSSAGTVNLEERQRP---VYDEESWTDVDFCRRVKMtg 165
Cdd:PLN02662  83 TASPFYHDVTDPQAELIDPAVKGTLNVLRSCAKVPSVKRVVVTSSMAAVAYNGKPLTpdvVVDETWFSDPAFCEESKL-- 160

                        170
                 ....*....|
gi 4097133   166 WmYFVSKTLA 175
Cdd:PLN02662 161 W-YVLSKTLA 169

cinnamyl-alcohol dehydrogenase

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4097133     1 MEGGAGASEKGTVLVTGASGFVGSWLVMKLLQAGYTVRATVRDPAnvgKTKPLMDLPGATERLSIWKADLAEEGSFHDAI 80
Cdd:PLN02896   1 MELEGRESATGTYCVTGATGYIGSWLVKLLLQRGYTVHATLRDPA---KSLHLLSKWKEGDRLRLFRADLQEEGSFDEAV 77

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4097133    81 RGCTGVFHVATPMDF-LSKDPEN-------EVIKPTVEGMISIMRACKEAGTVRRIVFTSSAGTVNLE---ERQRPVYDE 149
Cdd:PLN02896  78 KGCDGVFHVAASMEFdVSSDHNNieeyvqsKVIDPAIKGTLNVLKSCLKSKTVKRVVFTSSISTLTAKdsnGRWRAVVDE 157

                        170       180
                 ....*....|....*....|....*
gi 4097133   150 ESWTDVDFCRRVKMTGWMYFVSKTL 174
Cdd:PLN02896 158 TCQTPIDHVWNTKASGWVYVLSKLL 182

cinnamyl-alcohol dehydrogenase family protein

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4097133    13 VLVTGASGFVGSWLVMKLLQAGYTVRATVRDPANVGKTKPLMDLPGATERLSIWKADLAEEGSFHDAIRGCTGVFHVATP 92
Cdd:PLN02986   8 VCVTGASGYIASWIVKLLLLRGYTVKATVRDLTDRKKTEHLLALDGAKERLKLFKADLLEESSFEQAIEGCDAVFHTASP 87

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4097133    93 MDFLSKDPENEVIKPTVEGMISIMRACKEAGTVRRIVFTSSAGTVNLeeRQRP-----VYDEESWTDVDFCRRVKmtGWm 167
Cdd:PLN02986  88 VFFTVKDPQTELIDPALKGTINVLNTCKETPSVKRVILTSSTAAVLF--RQPPieandVVDETFFSDPSLCRETK--NW- 162

                 ....*...
gi 4097133   168 YFVSKTLA 175
Cdd:PLN02986 163 YPLSKILA 170

cinnamoyl-CoA reductase

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4097133     7 ASEKG-TVLVTGASGFVGSWLVMKLLQAGYTVRATVRDPANVGKTKpLMDLPGATERLSIWKADLAEEGSFHDAIRGCTG 85
Cdd:PLN02214   6 ASPAGkTVCVTGAGGYIASWIVKILLERGYTVKGTVRNPDDPKNTH-LRELEGGKERLILCKADLQDYEALKAAIDGCDG 84

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 4097133    86 VFHVATPmdfLSKDPEnEVIKPTVEGMISIMRACKEAgTVRRIVFTSSAGTVNLEERQRP--VYDEESWTDVDFCRRVK 162
Cdd:PLN02214  85 VFHTASP---VTDDPE-QMVEPAVNGAKFVINAAAEA-KVKRVVITSSIGAVYMDPNRDPeaVVDESCWSDLDFCKNTK 158

Nucleoside-diphosphate-sugar epimerase [Cell wall/membrane/envelope biogenesis];

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4097133   12 TVLVTGASGFVGSWLVMKLLQAGYTVRATVRDPAnvgKTKPLMDLPGATerlsIWKADLAEEGSFHDAIRGCTGVFHVAT 91
Cdd:COG0451   1 RILVTGGAGFIGSHLARRLLARGHEVVGLDRSPP---GAANLAALPGVE----FVRGDLRDPEALAAALAGVDAVVHLAA 73

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*
gi 4097133   92 PMDFLSKDPEnEVIKPTVEGMISIMRACKEAGtVRRIVFTSSAGT 136
Cdd:COG0451  74 PAGVGEEDPD-ETLEVNVEGTLNLLEAARAAG-VKRFVYASSSSV 116

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4097133   12 TVLVTGASGFVGSWLVMKLLQAGYTVRATVRDPANVGKTKPlmdlPGATerlsIWKADLAEEGSFHDAIRGCTGVFHVAT 91
Cdd:COG0702   1 KILVTGATGFIGRRVVRALLARGHPVRALVRDPEKAAALAA----AGVE----VVQGDLDDPESLAAALAGVDAVFLLVP 72

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*
gi 4097133   92 PMDflSKDPENEvikptVEGMISIMRACKEAGtVRRIVFTSSAGT 136
Cdd:COG0702  73 SGP--GGDFAVD-----VEGARNLADAAKAAG-VKRIVYLSALGA 109

UDP-glucose 4 epimerase, subgroup 4, extended (e) SDRs; UDP-glucose 4 epimerase (aka UDP-galactose-4-epimerase), is a homodimeric extended SDR. It catalyzes the NAD-dependent conversion of UDP-galactose to UDP-glucose, the final step in Leloir galactose synthesis. This subgroup is comprised of bacterial proteins, and includes the Staphylococcus aureus capsular polysaccharide Cap5N, which may have a role in the synthesis of UDP-N-acetyl-d-fucosamine. This subgroup has the characteristic active site tetrad and NAD-binding motif of the extended SDRs. Extended SDRs 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. 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. 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. 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 4097133   12 TVLVTGASGFVGSWLVMKLLQAGYTVRATVRDPANVGKTKPLMDLPGATerlsiwkadlaeegSFHDAIRGCTGVFHVAT 91
Cdd:cd05232   1 KVLVTGANGFIGRALVDKLLSRGEEVRIAVRNAENAEPSVVLAELPDID--------------SFTDLFLGVDAVVHLAA 66

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 4097133   92 ---PMDFLSKDPENEVIKPTVEGMISIMRACKEAGtVRRIVFTSSAgTVNLEERQRPVYDEES 151
Cdd:cd05232  67 rvhVMNDQGADPLSDYRKVNTELTRRLARAAARQG-VKRFVFLSSV-KVNGEGTVGAPFDETD 127

Putative NADH-flavin reductase [General function prediction only];

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4097133   13 VLVTGASGFVGSWLVMKLLQAGYTVRATVRDPANvgktkplmdLPGATERLSIWKADLAEEGSFHDAIRGCTGVFHVATP 92
Cdd:COG2910   2 IAVIGATGRVGSLIVREALARGHEVTALVRNPEK---------LPDEHPGLTVVVGDVLDPAAVAEALAGADAVVSALGA 72

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....
gi 4097133   93 mdflSKDPENEVIkptVEGMISIMRACKEAGtVRRIVFTSSAGT 136
Cdd:COG2910  73 ----GGGNPTTVL---SDGARALIDAMKAAG-VKRLIVVGGAGS 108

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 4097133   12 TVLVTGASGFVGSWLVMKLLQAGYTVRATVRDPANVGKTKPlmdlPGATerlsIWKADLAEEGSFHDAIRGCTGVFHVA- 90
Cdd:cd05243   1 KVLVVGATGKVGRHVVRELLDRGYQVRALVRDPSQAEKLEA----AGAE----VVVGDLTDAESLAAALEGIDAVISAAg 72

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 4097133   91 -TPMDflSKDPEnevikpTV--EGMISIMRACKEAGtVRRIVFTSSAGTVNLE---ERQRPVYDE 149
Cdd:cd05243  73 sGGKG--GPRTE------AVdyDGNINLIDAAKKAG-VKRFVLVSSIGADKPShplEALGPYLDA 128

atypical (a) SDRs, subgroup 2; This subgroup contains atypical SDRs, one member is identified as Escherichia coli protein ybjT, function unknown. Atypical SDRs are distinct from classical SDRs. Members of this subgroup have a glycine-rich NAD(P)-binding motif consensus that generally matches the extended SDRs, TGXXGXXG, but lacks the characteristic active site residues of the SDRs. This subgroup has basic residues (HXXXR) in place of the active site motif YXXXK, these may have a catalytic role. 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 4097133   13 VLVTGASGFVGSWLVMKLLQAGYTVRATVRDPANvgktkpLMDLPGAtERLSIWKADLAEEGSFHDAIRGCTGVFHVATP 92
Cdd:cd05245   1 VLVTGATGYVGGRLVPRLLQEGHQVRALVRSPEK------LADRPWS-ERVTVVRGDLEDPESLRAALEGIDTAYYLVHS 73

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*
gi 4097133   93 M----DFLSKDPenevikptvEGMISIMRACKEAGtVRRIVFTSS 133
Cdd:cd05245  74 MgsggDFEEADR---------RAARNFARAARAAG-VKRIIYLGG 108

3-beta hydroxysteroid dehydrogenase/isomerase family; The enzyme 3 beta-hydroxysteroid dehydrogenase/5-ene-4-ene isomerase (3 beta-HSD) catalyzes the oxidation and isomerization of 5-ene-3 beta-hydroxypregnene and 5-ene-hydroxyandrostene steroid precursors into the corresponding 4-ene-ketosteroids necessary for the formation of all classes of steroid hormones.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4097133     14 LVTGASGFVGSWLVMKLLQAG--YTVRAtvrdpANVGKTKPLMDLPGATERLSIWKADLAEEGSFHDAIRGCTGVFHVAT 91
Cdd:pfam01073   1 VVTGGGGFLGRHIIKLLVREGelKEVRV-----FDLRESPELLEDFSKSNVIKYIQGDVTDKDDLDNALEGVDVVIHTAS 75

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 4097133     92 PMDFLSKDPENEVIKPTVEGMISIMRACKEAGtVRRIVFTSSAGTVNLEERQRPVYD-EESW 152
Cdd:pfam01073  76 AVDVFGKYTFDEIMKVNVKGTQNVLEACVKAG-VRVLVYTSSAEVVGPNSYGQPILNgDEET 136

human NSDHL (NAD(P)H steroid dehydrogenase-like protein)-like, extended (e) SDRs; This subgroup includes human NSDHL and related proteins. These proteins have the characteristic active site tetrad of extended SDRs, and also have a close match to their NAD(P)-binding motif. Human NSDHL is a 3beta-hydroxysteroid dehydrogenase (3 beta-HSD) which functions in the cholesterol biosynthetic pathway. 3 beta-HSD catalyzes the oxidative conversion of delta 5-3 beta-hydroxysteroids to the delta 4-3-keto configuration; this activity is essential for the biosynthesis of all classes of hormonal steroids. Mutations in the gene encoding NSDHL cause CHILD syndrome (congenital hemidysplasia with ichthyosiform nevus and limb defects), an X-linked dominant, male-lethal trait. This subgroup also includes an unusual bifunctional [3beta-hydroxysteroid dehydrogenase (3b-HSD)/C-4 decarboxylase from Arabidopsis thaliana, and Saccharomyces cerevisiae ERG26, a 3b-HSD/C-4 decarboxylase, involved in the synthesis of ergosterol, the major sterol of yeast. Extended SDRs 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. 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. 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. Complex (multidomain) SDRs such as ketoreductase domains of fatty acid sythase 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 4097133   12 TVLVTGASGFVGSWLVMKLLQAG-YTVRAtvrdpANVGKTkpLMDLPGATERLSIWKADLAEEGSFHDAIR--GCTGVFH 88
Cdd:cd09813   1 SCLVVGGSGFLGRHLVEQLLRRGnPTVHV-----FDIRPT--FELDPSSSGRVQFHTGDLTDPQDLEKAFNekGPNVVFH 73

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*....
gi 4097133   89 VATPMDFLSKDPENEVIkptVEGMISIMRACKEAGtVRRIVFTSSAGTV 137
Cdd:cd09813  74 TASPDHGSNDDLYYKVN---VQGTRNVIEACRKCG-VKKLVYTSSASVV 118

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 4097133   12 TVLVTGASGFVGSWLVMKLLQAGYTVRATVRDPANVGKTKPLMDLPGaterLSIWKADLAEEGSFHDAIRGCTGVFHVAT 91
Cdd:cd05271   2 VVTVFGATGFIGRYVVNRLAKRGSQVIVPYRCEAYARRLLVMGDLGQ----VLFVEFDLRDDESIRKALEGSDVVINLVG 77

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....
gi 4097133   92 pMDFLSKDPENEVIKptVEGMISIMRACKEAGtVRRIVFTSSAG 135
Cdd:cd05271  78 -RLYETKNFSFEDVH--VEGPERLAKAAKEAG-VERLIHISALG 117

CDP-D-glucose 4,6-dehydratase, extended (e) SDRs; This subgroup contains CDP-D-glucose 4,6-dehydratase, an extended SDR, which catalyzes the conversion of CDP-D-glucose to CDP-4-keto-6-deoxy-D-glucose. This subgroup has the characteristic active site tetrad and NAD-binding motif of the extended SDRs. Extended SDRs 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. 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. 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. 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 4097133   12 TVLVTGASGFVGSWLVMKLLQAGYTVRATVRDPanvgKTKP-LMDLPGATERLSIWKADLAEEGSFHDAIRGCTG--VFH 88
Cdd:cd05252   6 RVLVTGHTGFKGSWLSLWLQELGAKVIGYSLDP----PTNPnLFELANLDNKISSTRGDIRDLNALREAIREYEPeiVFH 81

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*..
gi 4097133   89 VAT-PMDFLS-KDPEnEVIKPTVEGMISIMRACKEAGTVRRIVFTSS 133
Cdd:cd05252  82 LAAqPLVRLSyKDPV-ETFETNVMGTVNLLEAIRETGSVKAVVNVTS 127

extended (e) SDRs; Extended SDRs 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. 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. 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. 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 4097133   13 VLVTGASGFVGSWLVMKLLQAGYTVRATVRDpanvgktkplmdlpgaterlsiwkadlaeegsfhdairgcTGVFH-VAT 91
Cdd:cd08946   1 ILVTGGAGFIGSHLVRRLLERGHEVVVIDRL----------------------------------------DVVVHlAAL 40

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4097133   92 PMDFLSKDPENEVIKPTVEGMISIMRACKEAGtVRRIVFTSSAGtvnleerqrpVYDEESWTDVDFCRRVKmTGWMYFVS 171
Cdd:cd08946  41 VGVPASWDNPDEDFETNVVGTLNLLEAARKAG-VKRFVYASSAS----------VYGSPEGLPEEEETPPR-PLSPYGVS 108

                ....
gi 4097133  172 KTLA 175
Cdd:cd08946 109 KLAA 112

atypical (a) SDRs, subgroup 7; This subgroup contains atypical SDRs of unknown function. Members of this subgroup have a glycine-rich NAD(P)-binding motif consensus that matches the extended SDRs, TGXXGXXG, but lacks the characteristic active site residues of the SDRs. This subgroup has basic residues (HXXXR) in place of the active site motif YXXXK, these may have a catalytic role. 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 4097133   13 VLVTGASGFVGSWLVMKLLQAGYTVRATVRDPANVGKTKPlmdlPGAterlSIWKADLAEEGSFHDAIRGCTGVFHVATP 92
Cdd:cd05262   3 VFVTGATGFIGSAVVRELVAAGHEVVGLARSDAGAAKLEA----AGA----QVHRGDLEDLDILRKAAAEADAVIHLAFT 74

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*..
gi 4097133   93 MDFLSKDPENEVIKPtvegmisIMRACKEA--GTVRRIVFTSSAGTV 137
Cdd:cd05262  75 HDFDNFAQACEVDRR-------AIEALGEAlrGTGKPLIYTSGIWLL 114

Arna decarboxylase_like, extended (e) SDRs; Decarboxylase domain of ArnA. ArnA, is an enzyme involved in the modification of outer membrane protein lipid A of gram-negative bacteria. It is a bifunctional enzyme that catalyzes the NAD-dependent decarboxylation of UDP-glucuronic acid and N-10-formyltetrahydrofolate-dependent formylation of UDP-4-amino-4-deoxy-l-arabinose; its NAD-dependent decaboxylating activity is in the C-terminal 360 residues. This subgroup belongs to the extended SDR family, however the NAD binding motif is not a perfect match and the upstream Asn of the canonical active site tetrad is not conserved. Extended SDRs 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. 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. 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. 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 4097133   12 TVLVTGASGFVGSWLVMKLLQAGYTVRATvrDPANVGKTKPLMDLPGaTERLSIWKADLAEEGSFHDAIRGCTGVFHVAT 91
Cdd:cd05257   1 NVLVTGADGFIGSHLTERLLREGHEVRAL--DIYNSFNSWGLLDNAV-HDRFHFISGDVRDASEVEYLVKKCDVVFHLAA 77

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*
gi 4097133   92 PM--DFLSKDPEnEVIKPTVEG-MISIMRACKEAgtVRRIVFTSS 133
Cdd:cd05257  78 LIaiPYSYTAPL-SYVETNVFGtLNVLEAACVLY--RKRVVHTST 119