atypical (a) SDRs, subgroup 8; This subgroup contains atypical SDRs of unknown function. Proteins in this subgroup have a glycine-rich NAD(P)-binding motif consensus that resembles that of the extended SDRs, (GXXGXXG or GGXGXXG), but lacks the characteristic active site residues of the SDRs. A Cys often replaces the usual Lys of the YXXXK active site motif, while the upstream Ser is generally present and Arg replaces the usual Asn. 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 2768069671   2 KVVIAGSSGLIGTALVAALRRDGHEVSRLVRRAPAA---PDEYAWDPAraQLDERALRGADAVVNLCGASIGARRWNGSY 78
Cdd:cd05242     1 KIVITGGTGFIGRALTRRLTAAGHEVVVLSRRPGKAeglAEVITWDGL--SLGPWELPGADAVINLAGEPIACRRWTEAN 78

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2768069671  79 KQLLRDSRITPTDVLATAVAAAGVP--TLVNASGVHYYGgDTGNAVVDETSPAGTGFLATLCRDWEAATEPASSAGVRTV 156
Cdd:cd05242    79 KKEILSSRIESTRVLVEAIANAPAPpkVLISASAVGYYG-HSGDEVLTENSPSGKDFLAEVCKAWEKAAQPASELGTRVV 157

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2768069671 157 LVRSAVVLARNGGMLSMLHPLYWLGLGGRLGSGRQYTPWVSLDDEIGAIVFALTHPEISGPINSAGPAPVTYAEFNRALG 236
Cdd:cd05242   158 ILRTGVVLGPDGGALPKMLLPFRLGLGGPLGSGRQWMSWIHIDDLVRLIEFAIENPDLSGPVNAVAPNPVTNAEFTKALG 237

                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 2768069671 237 RALRRPTPFVVPGFALRALVGEFADEAILHGPRAIPAALEQAGYTFQHPTIGAALAAAV 295
Cdd:cd05242   238 RALHRPAGLPVPAFALKLGFGEMRAELLLKGQRVLPERLLDAGFQFRYPDLEEALEELL 296

Domain of unknown function (DUF1731); This domain of unknown function appears towards the C-terminus of proteins of the NAD dependent epimerase/dehydratase family (pfam01370) in bacteria, eukaryotes and archaea. Many of the proteins in which it is found are involved in cell-division inhibition.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*..
gi 2768069671 247 VPGFALRALVGEFADEaILHGPRAIPAALEQAGYTFQHPTIGAALAA 293
Cdd:pfam08338   1 VPAFALRLLLGEMAEL-LLEGQRVLPKRLLEAGFQFRYPDLEEALRD 46

atypical (a) SDRs, subgroup 8; This subgroup contains atypical SDRs of unknown function. Proteins in this subgroup have a glycine-rich NAD(P)-binding motif consensus that resembles that of the extended SDRs, (GXXGXXG or GGXGXXG), but lacks the characteristic active site residues of the SDRs. A Cys often replaces the usual Lys of the YXXXK active site motif, while the upstream Ser is generally present and Arg replaces the usual Asn. 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 2768069671   2 KVVIAGSSGLIGTALVAALRRDGHEVSRLVRRAPAA---PDEYAWDPAraQLDERALRGADAVVNLCGASIGARRWNGSY 78
Cdd:cd05242     1 KIVITGGTGFIGRALTRRLTAAGHEVVVLSRRPGKAeglAEVITWDGL--SLGPWELPGADAVINLAGEPIACRRWTEAN 78

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2768069671  79 KQLLRDSRITPTDVLATAVAAAGVP--TLVNASGVHYYGgDTGNAVVDETSPAGTGFLATLCRDWEAATEPASSAGVRTV 156
Cdd:cd05242    79 KKEILSSRIESTRVLVEAIANAPAPpkVLISASAVGYYG-HSGDEVLTENSPSGKDFLAEVCKAWEKAAQPASELGTRVV 157

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2768069671 157 LVRSAVVLARNGGMLSMLHPLYWLGLGGRLGSGRQYTPWVSLDDEIGAIVFALTHPEISGPINSAGPAPVTYAEFNRALG 236
Cdd:cd05242   158 ILRTGVVLGPDGGALPKMLLPFRLGLGGPLGSGRQWMSWIHIDDLVRLIEFAIENPDLSGPVNAVAPNPVTNAEFTKALG 237

                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 2768069671 237 RALRRPTPFVVPGFALRALVGEFADEAILHGPRAIPAALEQAGYTFQHPTIGAALAAAV 295
Cdd:cd05242   238 RALHRPAGLPVPAFALKLGFGEMRAELLLKGQRVLPERLLDAGFQFRYPDLEEALEELL 296

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2768069671   2 KVVIAGSSGLIGTALVAALRRDGHEVSRLVRRAPAAPDEYAWDPARA-QLD-------ERALRGADAVVNLcGASIGARR 73
Cdd:COG0451     1 RILVTGGAGFIGSHLARRLLARGHEVVGLDRSPPGAANLAALPGVEFvRGDlrdpealAAALAGVDAVVHL-AAPAGVGE 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2768069671  74 WNGsykQLLRDSRITPTDVLATAVAAAGVPTLVNASGVHYYGGDTGnaVVDETSPAGTGFL--ATLCRDWEAATEPASSA 151
Cdd:COG0451    80 EDP---DETLEVNVEGTLNLLEAARAAGVKRFVYASSSSVYGDGEG--PIDEDTPLRPVSPygASKLAAELLARAYARRY 154

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2768069671 152 GVRTVLVRSAVVLARNGGML--SMLHPLYWLGLGGRLGSGRQYTPWVSLDDEIGAIVFALTHPEISG-PINSAGPAPVTY 228
Cdd:COG0451   155 GLPVTILRPGNVYGPGDRGVlpRLIRRALAGEPVPVFGDGDQRRDFIHVDDVARAIVLALEAPAAPGgVYNVGGGEPVTL 234

                         250       260
                  ....*....|....*....|
gi 2768069671 229 AEFNRALGRALRRPTPFVVP 248
Cdd:COG0451   235 RELAEAIAEALGRPPEIVYP 254

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 2768069671   2 KVVIAGSSGLIGTALVAALRRDGHEVSRLVRRA-PAAPDEYAWDPARAQLDERALRGADAVVNLCGASIGARRWNGSYKQ 80
Cdd:cd05232     1 KVLVTGANGFIGRALVDKLLSRGEEVRIAVRNAeNAEPSVVLAELPDIDSFTDLFLGVDAVVHLAARVHVMNDQGADPLS 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2768069671  81 LLRDSRITPTDVLATAVAAAGVPTLVNASGVHYYGGDTGNAVVDETSPA------GTGflatlcrDWEAA---TEPASSA 151
Cdd:cd05232    81 DYRKVNTELTRRLARAAARQGVKRFVFLSSVKVNGEGTVGAPFDETDPPapqdayGRS-------KLEAEralLELGASD 153

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2768069671 152 GVRTVLVRSAVVLARN--GGMLSMLHPLYWLGLGGRLGSGRQYTpWVSLDDEIGAIVFALTHPEISGPINSAG-PAPVTY 228
Cdd:cd05232   154 GMEVVILRPPMVYGPGvrGNFARLMRLIDRGLPLPPGAVKNRRS-LVSLDNLVDAIYLCISLPKAANGTFLVSdGPPVST 232

                         250       260
                  ....*....|....*....|....*.
gi 2768069671 229 AEFNRALGRALRRPTP-FVVPGFALR 253
Cdd:cd05232   233 AELVDEIRRALGKPTRlLPVPAGLLR 258

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2768069671   2 KVVIAGSSGLIGTALVAALRRDGHEVSRLVRRAPAAPDEYAWDPARAQLD-------ERALRGADAVVNLCGASIGARrw 74
Cdd:COG0702     1 KILVTGATGFIGRRVVRALLARGHPVRALVRDPEKAAALAAAGVEVVQGDlddpeslAAALAGVDAVFLLVPSGPGGD-- 78

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2768069671  75 ngsykqllRDSRITPTDVLATAVAAAGVPTLVNASGVHyyggdtgnavVDETSPAGTGflatlcrDWEAATEPA-SSAGV 153
Cdd:COG0702    79 --------FAVDVEGARNLADAAKAAGVKRIVYLSALG----------ADRDSPSPYL-------RAKAAVEEAlRASGL 133

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2768069671 154 RTVLVRSAVVLARNGGMLSML--HPLYWLGLGGRLgsgrqyTPWVSLDDEIGAIVFALTHPEISG---PInsAGPAPVTY 228
Cdd:COG0702   134 PYTILRPGWFMGNLLGFFERLreRGVLPLPAGDGR------VQPIAVRDVAEAAAAALTDPGHAGrtyEL--GGPEALTY 205

                         250
                  ....*....|
gi 2768069671 229 AEFNRALGRA 238
Cdd:COG0702   206 AELAAILSEA 215

UDP-glucose 4 epimerase (G4E), subgroup 3, extended (e) SDRs; Members of this bacterial subgroup are identified as possible sugar epimerases, such as UDP-glucose 4 epimerase. However, while the NAD(P)-binding motif is fairly well conserved, not all members retain the canonical active site tetrad of the extended 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. 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 2768069671   3 VVIAGSSGLIGTALVAALRRD--GHEVSRLVRRAPAAPDE----YAWDPARAQLDER-ALRGADAVVNLcgASIGARRWN 75
Cdd:cd05240     1 ILVTGAAGGLGRLLARRLAASprVIGVDGLDRRRPPGSPPkveyVRLDIRDPAAADVfREREADAVVHL--AFILDPPRD 78

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2768069671  76 GSykqLLRDSRITPTDVLATAVAAAGVPTLVNASGVHYYGGDTGNAVV-DETSPAGTGFLATLCRDWE-----AATEPAS 149
Cdd:cd05240    79 GA---ERHRINVDGTQNVLDACAAAGVPRVVVTSSVAVYGAHPDNPAPlTEDAPLRGSPEFAYSRDKAeveqlLAEFRRR 155

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2768069671 150 SAGVRTVLVRSAVVLARNG--GMLSMLHPLYWLGLGGRLGsgrqytPWVSL--DDEIGAIVFALThPEISGPINSAGPAP 225
Cdd:cd05240   156 HPELNVTVLRPATILGPGTrnTTRDFLSPRRLPVPGGFDP------PFQFLheDDVARALVLAVR-AGATGIFNVAGDGP 228

                         250       260       270
                  ....*....|....*....|....*....|.
gi 2768069671 226 VTYAEFNRALG-RALRRPTPFVVPGFALRAL 255
Cdd:cd05240   229 VPLSLVLALLGrRPVPLPSPLPAALAAARRL 259

NAD dependent epimerase/dehydratase family; This family of proteins utilize NAD as a cofactor. The proteins in this family use nucleotide-sugar substrates for a variety of chemical reactions.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2768069671   3 VVIAGSSGLIGTALVAALRRDGHEVSRLVRRAPAAPDEYAWDPARAQLD-------ERALR--GADAVVNLcgASIGARR 73
Cdd:pfam01370   1 ILVTGATGFIGSHLVRRLLEKGYEVIGLDRLTSASNTARLADLRFVEGDltdrdalEKLLAdvRPDAVIHL--AAVGGVG 78

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*.
gi 2768069671  74 WNGSYKQLLRDSRITPTDVLATAVAAAGVPTLVNASGVHYYGGDTG 119
Cdd:pfam01370  79 ASIEDPEDFIEANVLGTLNLLEAARKAGVKRFLFASSSEVYGDGAE 124

uncharacterized subgroup of aldehyde reductase and flavonoid reductase related proteins, extended (e) SDRs; This subgroup contains proteins of unknown function related to aldehyde reductase and flavonoid reductase of the extended SDR-type. Aldehyde reductase I (aka carbonyl reductase) is an NADP-binding SDR; it has an NADP-binding motif consensus that is slightly different from the canonical SDR form and lacks the Asn of the extended SDR active site tetrad. Aldehyde reductase I catalyzes the NADP-dependent reduction of ethyl 4-chloro-3-oxobutanoate to ethyl (R)-4-chloro-3-hydroxybutanoate. The related flavonoid reductases act in the NADP-dependent reduction of flavonoids, ketone-containing plant secondary metabolites. 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 2768069671   3 VVIAGSSGLIGTALVAALRRDGHEVSRLVRRA------PAAPDEYAW-DPARAQLDERALRGADAVVNLCG-ASIGARRW 74
Cdd:cd05228     1 ILVTGATGFLGSNLVRALLAQGYRVRALVRSGsdavllDGLPVEVVEgDLTDAASLAAAMKGCDRVFHLAAfTSLWAKDR 80

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....
gi 2768069671  75 ngsykQLLRDSRITPTDVLATAVAAAGVPTLVNASGVHYYGGDTGnAVVDETSP 128
Cdd:cd05228    81 -----KELYRTNVEGTRNVLDAALEAGVRRVVHTSSIAALGGPPD-GRIDETTP 128

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 2768069671   1 MKVVIAGSSGLIGTALVAALRRDGHEVSRLVRRAPAAPDEYAW--DPARAQLDE-----RALRGADAVVNLcgasiGARR 73
Cdd:cd05262     1 MKVFVTGATGFIGSAVVRELVAAGHEVVGLARSDAGAAKLEAAgaQVHRGDLEDldilrKAAAEADAVIHL-----AFTH 75

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2768069671  74 WNGSYKQLLR-DSRItpTDVLATAVAAAGVPtLVNASGVHYYGGDTGNAVVDETS-PAGTGFLATLCrdwEAATEPASSA 151
Cdd:cd05262    76 DFDNFAQACEvDRRA--IEALGEALRGTGKP-LIYTSGIWLLGPTGGQEEDEEAPdDPPTPAARAVS---EAAALELAER 149

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2768069671 152 GVR-TVLVRSAVVLAR-NGGMLSMLhplywlGLGGRLGSGRQYT-------PWVSLDDEIGAIVFALTHPEISGPINSAG 222
Cdd:cd05262   150 GVRaSVVRLPPVVHGRgDHGFVPML------IAIAREKGVSAYVgdgknrwPAVHRDDAARLYRLALEKGKAGSVYHAVA 223

                         250       260       270       280       290       300
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 2768069671 223 PAPVTYAEFNRALGRALRRPTPfVVPGFALRALVGEFADEAILHGPRAIPAALEQAGYTFQHPTI 287
Cdd:cd05262   224 EEGIPVKDIAEAIGRRLGVPVV-SIPAEEAAAHFGWLAMFVALDQPVSSQKTRRRLGWKPQQPSL 287

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 2768069671   2 KVVIAGSSGLIGTALVAALRRDGHEVSRLVRRAPAAPDEYAW------DPARAQLDERALRGADAVVNlcgaSIGARRWN 75
Cdd:cd05244     1 KIAIIGATGRTGSAIVREALARGHEVTALVRDPAKLPAEHEKlkvvqgDVLDLEDVKEALEGQDAVIS----ALGTRNDL 76

                          90       100       110
                  ....*....|....*....|....*....|.
gi 2768069671  76 GSYKQLlrdsrITPTDVLATAVAAAGVPTLV 106
Cdd:cd05244    77 SPTTLH-----SEGTRNIVSAMKAAGVKRLI 102

sugar epimerase family protein;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2768069671   1 MKVVIAGSSGLIGTALVAALRRDGHEVSRLVRRAPAApdeyaWdPARAQLDERALRGADAVvnlcgasigarrwngsykq 80
Cdd:PRK05865    1 MRIAVTGASGVLGRGLTARLLSQGHEVVGIARHRPDS-----W-PSSADFIAADIRDATAV------------------- 55

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2768069671  81 llrDSRITPTDVLATAVAAAGVPTLVNASGvhyyggdTGNaVVDETSPAGTGFLATLCRDWEAATEPA-SSAGVRTVLVR 159
Cdd:PRK05865   56 ---ESAMTGADVVAHCAWVRGRNDHINIDG-------TAN-VLKAMAETGTGRIVFTSSGHQPRVEQMlADCGLEWVAVR 124

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2768069671 160 SAVVLARNggmLSMLHPLYWLGLGGRLGSGRQYTPWVSLDDEIGAIVFALTHPEI-SGPINSAGPAPVTYaefnRALGRA 238
Cdd:PRK05865  125 CALIFGRN---VDNWVQRLFALPVLPAGYADRVVQVVHSDDAQRLLVRALLDTVIdSGPVNLAAPGELTF----RRIAAA 197

                         250       260       270
                  ....*....|....*....|....*....|....*..
gi 2768069671 239 LRRPT-PFVVPGFALRALVGEFA--------DEAILH 266
Cdd:PRK05865  198 LGRPMvPIGSPVLRRVTSFAELEllhsaplmDVTLLR 234

phenylcoumaran benzylic ether reductase (PCBER) like, atypical (a) SDRs; PCBER and pinoresinol-lariciresinol reductases are NADPH-dependent aromatic alcohol reductases, and are atypical members of the SDR family. Other proteins in this subgroup are identified as eugenol synthase. These proteins contain an N-terminus characteristic of NAD(P)-binding proteins and a small C-terminal domain presumed to be involved in substrate binding, but they do not have the conserved active site Tyr residue typically found in SDRs. Numerous other members have unknown functions. The glycine rich NADP-binding motif in this subgroup is of 2 forms: GXGXXG and G[GA]XGXXG; it tends to be atypical compared with the forms generally seen in classical or extended SDRs. The usual SDR active site tetrad is not present, but a critical active site Lys at the usual SDR position has been identified in various members, though other charged and polar residues are found at this position in this subgroup. Atypical SDR-related proteins retain the Rossmann fold of the SDRs, but have limited sequence identity and generally lack the catalytic properties of the archetypical members. 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 2768069671   2 KVVIAGSSGLIGTALVAAL-RRDGHEVSRLVRraPAAPDEYAWDPARAQLDER----------ALRGADAVVNLCGASig 70
Cdd:cd05259     1 KIAIAGATGTLGGPIVSALlASPGFTVTVLTR--PSSTSSNEFQPSGVKVVPVdyasheslvaALKGVDAVISALGGA-- 76

                          90       100       110
                  ....*....|....*....|....*....|...
gi 2768069671  71 arrwnGSYKQLlrdsritptdVLATAVAAAGVP 103
Cdd:cd05259    77 -----AIGDQL----------KLIDAAIAAGVK 94

atypical (a) SDRs, subgroup 1; Atypical SDRs in this subgroup are poorly defined and have been identified putatively as isoflavones reductase, sugar dehydratase, mRNA binding protein etc. Atypical SDRs are distinct from classical SDRs. Members of this subgroup retain the canonical active site triad (though not the upstream Asn found in most SDRs) but have an unusual putative glycine-rich NAD(P)-binding motif, GGXXXXG, in the usual location. 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 2768069671   1 MKVVIAGSSGLIGTALVAALRRDGHEVSRLVR--RAPAAPDEYawdparaqldeRALRGADAVVNLCGASIGARRWNGSY 78
Cdd:cd05265     1 MKILIIGGTRFIGKALVEELLAAGHDVTVFNRgrTKPDLPEGV-----------EHIVGDRNDRDALEELLGGEDFDVVV 69

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2768069671  79 KQLLRdsriTPTDVLATAVAAAG-VPTLVNASGVHYYGgdTGNAVVDETSPAGTGFLATLCRDW-----EAATEPA--SS 150
Cdd:cd05265    70 DTIAY----TPRQVERALDAFKGrVKQYIFISSASVYL--KPGRVITESTPLREPDAVGLSDPWdygrgKRAAEDVliEA 143

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2768069671 151 AGVRTVLVRSAVVLarngGMLSMLHPLYW-----LGLGGRLGSGRQYTPW--VSLDDEIGAIVFALTHPE-ISGPINSAG 222
Cdd:cd05265   144 AAFPYTIVRPPYIY----GPGDYTGRLAYffdrlARGRPILVPGDGHSLVqfIHVKDLARALLGAAGNPKaIGGIFNITG 219

                         250
                  ....*....|....*..
gi 2768069671 223 PAPVTYAEFNRALGRAL 239
Cdd:cd05265   220 DEAVTWDELLEACAKAL 236