Rossmann-fold NAD(P)(+)-binding proteins; A large family of proteins that share a Rossmann-fold NAD(P)H/NAD(P)(+) binding (NADB) domain. The NADB domain is found in numerous dehydrogenases of metabolic pathways such as glycolysis, and many other redox enzymes. NAD binding involves numerous hydrogen-bonds and van der Waals contacts, in particular H-bonding of residues in a turn between the first strand and the subsequent helix of the Rossmann-fold topology. Characteristically, this turn exhibits a consensus binding pattern similar to GXGXXG, in which the first 2 glycines participate in NAD(P)-binding, and the third facilitates close packing of the helix to the beta-strand. Typically, proteins in this family contain a second domain in addition to the NADB domain, which is responsible for specifically binding a substrate and catalyzing a particular enzymatic reaction.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1440590402   1 MPYIAQVAVGRRESLAVFGNDYPTEDGTGVRDYIHVMDLADGHVAAMEKLADKAGVHIYNLGAGVGSSVLDVVNAFSKAC 80
Cdd:PRK10675  201 MPYIAQVAVGRRDSLAIFGNDYPTEDGTGVRDYIHVMDLADGHVAAMEKLANKPGVHIYNLGAGVGSSVLDVVNAFSKAC 280

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 1440590402  81 GKPINYHFAPRREGDLPAYWADAEKADRELNWRVTRNLDEMAQDTWHWQSRHPQGYPD 138
Cdd:PRK10675  281 GKPVNYHFAPRREGDLPAYWADASKADRELNWRVTRTLDEMAQDTWHWQSRHPQGYPD 338

UDP-galactose-4-epimerase; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1440590402   1 MPYIAQVAVGRRESLAVFGNDYPTEDGTGVRDYIHVMDLADGHVAAMEKLADKAGVHIYNLGAGVGSSVLDVVNAFSKAC 80
Cdd:PRK10675  201 MPYIAQVAVGRRDSLAIFGNDYPTEDGTGVRDYIHVMDLADGHVAAMEKLANKPGVHIYNLGAGVGSSVLDVVNAFSKAC 280

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 1440590402  81 GKPINYHFAPRREGDLPAYWADAEKADRELNWRVTRNLDEMAQDTWHWQSRHPQGYPD 138
Cdd:PRK10675  281 GKPVNYHFAPRREGDLPAYWADASKADRELNWRVTRTLDEMAQDTWHWQSRHPQGYPD 338

UDP-glucose 4 epimerase, subgroup 1, 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 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 1440590402   1 MPYIAQVAVGRRESLAVFGNDYPTEDGTGVRDYIHVMDLADGHVAAMEKLADKAGVHIYNLGAGVGSSVLDVVNAFSKAC 80
Cdd:cd05247   194 IPYVLQVALGRREKLAIFGDDYPTPDGTCVRDYIHVVDLADAHVLALEKLENGGGSEIYNLGTGRGYSVLEVVEAFEKVS 273

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|
gi 1440590402  81 GKPINYHFAPRREGDLPAYWADAEKADRELNWRVTRNLDEMAQDTWHWQS 130
Cdd:cd05247   274 GKPIPYEIAPRRAGDPASLVADPSKAREELGWKPKRDLEDMCEDAWNWQS 323

GDP-mannose 4,6 dehydratase;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1440590402   1 MPYIAQVAVGRRESLAVfGNDYPTEDGTGVRDYIHVMDL------------ADGHVAAMEKLADKAGVHIYNLGAGVGSS 68
Cdd:pfam16363 195 TRGVARIKLGKQEKLYL-GNLDAKRDWGHARDYVEAMWLmlqqdkpddyviATGETHTVREFVEKAFLELGLTITWEGKG 273

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 1440590402  69 VldvvNAFSKACGKP-INYHFAPRREGDLPAYWADAEKADRELNWRVTRNLDEMAQDT 125
Cdd:pfam16363 274 E----IGYFKASGKVhVLIDPRYFRPGEVDRLLGDPSKAKEELGWKPKVSFEELVREM 327

UDP-galactose-4-epimerase; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1440590402   1 MPYIAQVAVGRRESLAVFGNDYPTEDGTGVRDYIHVMDLADGHVAAMEKLADKAGVHIYNLGAGVGSSVLDVVNAFSKAC 80
Cdd:PRK10675  201 MPYIAQVAVGRRDSLAIFGNDYPTEDGTGVRDYIHVMDLADGHVAAMEKLANKPGVHIYNLGAGVGSSVLDVVNAFSKAC 280

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 1440590402  81 GKPINYHFAPRREGDLPAYWADAEKADRELNWRVTRNLDEMAQDTWHWQSRHPQGYPD 138
Cdd:PRK10675  281 GKPVNYHFAPRREGDLPAYWADASKADRELNWRVTRTLDEMAQDTWHWQSRHPQGYPD 338

UDP-glucose 4 epimerase, subgroup 1, 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 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 1440590402   1 MPYIAQVAVGRRESLAVFGNDYPTEDGTGVRDYIHVMDLADGHVAAMEKLADKAGVHIYNLGAGVGSSVLDVVNAFSKAC 80
Cdd:cd05247   194 IPYVLQVALGRREKLAIFGDDYPTPDGTCVRDYIHVVDLADAHVLALEKLENGGGSEIYNLGTGRGYSVLEVVEAFEKVS 273

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|
gi 1440590402  81 GKPINYHFAPRREGDLPAYWADAEKADRELNWRVTRNLDEMAQDTWHWQS 130
Cdd:cd05247   274 GKPIPYEIAPRRAGDPASLVADPSKAREELGWKPKRDLEDMCEDAWNWQS 323

UDP-glucose-4-epimerase GalE; Alternate name: UDPgalactose 4-epimerase This enzyme interconverts UDP-glucose and UDP-galactose. A set of related proteins, some of which are tentatively identified as UDP-glucose-4-epimerase in Thermotoga maritima, Bacillus halodurans, and several archaea, but deeply branched from this set and lacking experimental evidence, are excluded from this model and described by a separate model. [Energy metabolism, Sugars]

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1440590402   1 MPYIAQVAVGRRESLAVFGNDYPTEDGTGVRDYIHVMDLADGHVAAMEKLADKAGVHIYNLGAGVGSSVLDVVNAFSKAC 80
Cdd:TIGR01179 196 IPYACQVAVGKRDKLTIFGTDYPTPDGTCVRDYIHVMDLADAHLAALEYLLNGGGSHVYNLGYGQGFSVLEVIEAFKKVS 275

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|...
gi 1440590402  81 GKPINYHFAPRREGDLPAYWADAEKADRELNWRVTR-NLDEMAQDTWHWQSRH 132
Cdd:TIGR01179 276 GKDFPVELAPRRPGDPASLVADASKIRRELGWQPKYtDLEEIIKDAWRWESRN 328

GDP-mannose 4,6 dehydratase;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1440590402   1 MPYIAQVAVGRRESLAVfGNDYPTEDGTGVRDYIHVMDL------------ADGHVAAMEKLADKAGVHIYNLGAGVGSS 68
Cdd:pfam16363 195 TRGVARIKLGKQEKLYL-GNLDAKRDWGHARDYVEAMWLmlqqdkpddyviATGETHTVREFVEKAFLELGLTITWEGKG 273

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 1440590402  69 VldvvNAFSKACGKP-INYHFAPRREGDLPAYWADAEKADRELNWRVTRNLDEMAQDT 125
Cdd:pfam16363 274 E----IGYFKASGKVhVLIDPRYFRPGEVDRLLGDPSKAKEELGWKPKVSFEELVREM 327

CDP-tyvelose 2-epimerase, extended (e) SDRs; CDP-tyvelose 2-epimerase is a tetrameric SDR that catalyzes the conversion of CDP-D-paratose to CDP-D-tyvelose, the last step in tyvelose biosynthesis. This subgroup is a member of the extended SDR subfamily, with a characteristic active site tetrad and NAD-binding 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 1440590402   3 YIAQVAVgRRESLAVFGNDyptedGTGVRDYIHVMDLADGHVAAMEKLADKAGvHIYNLGAGVGSSV--LDVVNAFSKAC 80
Cdd:cd05258   216 YFLKCAV-TGKPLTIFGYG-----GKQVRDVLHSADLVNLYLRQFQNPDRRKG-EVFNIGGGRENSVslLELIALCEEIT 288

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*....
gi 1440590402  81 GKPINYHFAPRREGDLPAYWADAEKADRELNWRVTRNLDEMAQDTWHWQ 129
Cdd:cd05258   289 GRKMESYKDENRPGDQIWYISDIRKIKEKPGWKPERDPREILAEIYAWI 337

UDP-glucose 4-epimerase (G4E), subgroup 5, extended (e) SDRs; This subgroup partially conserves the characteristic active site tetrad and NAD-binding motif of the extended SDRs, and has been identified as possible UDP-glucose 4-epimerase (aka UDP-galactose 4-epimerase), a homodimeric member of the extended SDR family. UDP-glucose 4-epimerase 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 1440590402  11 RRESLAVFGndypteDGTGVRDYIHVMDLADGHVAAmekLADKAGVHIYNLGAGVGSSVLDVVNAFSKACGKPINYHFAP 90
Cdd:cd05264   191 RGEPIEIWG------DGESIRDYIYIDDLVEALMAL---LRSKGLEEVFNIGSGIGYSLAELIAEIEKVTGRSVQVIYTP 261

                          90       100       110
                  ....*....|....*....|....*....|....*...
gi 1440590402  91 RREGDLPAYWADAEKADRELNWRVTRNLDEMAQDTWHW 128
Cdd:cd05264   262 ARTTDVPKIVLDISRARAELGWSPKISLEDGLEKTWQW 299

UDP glucuronic acid epimerase, extended (e) SDRs; This subgroup contains UDP-D-glucuronic acid 4-epimerase, an extended SDR, which catalyzes the conversion of UDP-alpha-D-glucuronic acid to UDP-alpha-D-galacturonic acid. This group has the SDR's canonical catalytic tetrad and the TGxxGxxG 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 1440590402  25 EDGTGVRDYIHVMDLADGHVAAMEKLADK---------------AGVHIYNLGAGVGSSVLDVVNAFSKACGKPINYHFA 89
Cdd:cd05253   210 NDGNMSRDFTYIDDIVEGVVRALDTPAKPnpnwdaeapdpstssAPYRVYNIGNNSPVKLMDFIEALEKALGKKAKKNYL 289

                          90       100       110
                  ....*....|....*....|....*....|.
gi 1440590402  90 PRREGDLPAYWADAEKADRELNWRVTRNLDE 120
Cdd:cd05253   290 PMQKGDVPETYADISKLQRLLGYKPKTSLEE 320

ADP-L-glycero-D-mannoheptose 6-epimerase (GME), extended (e) SDRs; This subgroup contains ADP-L-glycero-D-mannoheptose 6-epimerase, an extended SDR, which catalyzes the NAD-dependent interconversion of ADP-D-glycero-D-mannoheptose and ADP-L-glycero-D-mannoheptose. This subgroup has the canonical active site tetrad and NAD(P)-binding 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 1440590402   9 VGRRESLAVFGNDYPTEDGTGVRDYIHVMDLADGHVAAMEKlADKAGvhIYNLGAGVGSSVLDVVNAFSKACGKPINYHF 88
Cdd:cd05248   194 IKAGEKVKLFKSSDGYADGEQLRDFVYVKDVVKVNLFFLEN-PSVSG--IFNVGTGRARSFNDLASATFKALGKEVKIEY 270

                  ..
gi 1440590402  89 AP 90
Cdd:cd05248   271 ID 272

UDP-glucose 4 epimerase, subgroup 2, 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 archaeal and bacterial proteins, and 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 1440590402  11 RRESLAVFGndypteDGTGVRDYIHVMDLADGHVAAMEKlaDKAGVHIYNLGAGVGSSVLDVVNAFSKACGKPINYHFAP 90
Cdd:cd05234   192 NPNELEVLG------DGRQRKSYLYVSDCVDAMLLAWEK--STEGVNIFNLGNDDTISVNEIAEIVIEELGLKPRFKYSG 263

                          90       100       110
                  ....*....|....*....|....*....|...
gi 1440590402  91 -RR--EGDLPAYWADAEKAdRELNWRVTRNLDE 120
Cdd:cd05234   264 gDRgwKGDVPYMRLDIEKL-KALGWKPRYNSEE 295

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 1440590402  26 DGTGVRDYIHVMDLADGHVAAMekLADKAGVHIYNLGAGVGSSVLDVVNAFSK-ACGKPINYHFAPRREGDlPAY----- 99
Cdd:cd05257   206 DGSPTRDFNFVKDTARGFIDIL--DAIEAVGEIINNGSGEEISIGNPAVELIVeELGEMVLIVYDDHREYR-PGYsever 282

                          90       100       110
                  ....*....|....*....|....*....|....
gi 1440590402 100 -WADAEKADRELNWRVTRNLDEMAQDTWHWQSRH 132
Cdd:cd05257   283 rIPDIRKAKRLLGWEPKYSLRDGLRETIEWFKDQ 316

UDP-glucuronate decarboxylase (UGD) and related proteins, extended (e) SDRs; UGD catalyzes the formation of UDP-xylose from UDP-glucuronate; it is an extended-SDR, and has the characteristic glycine-rich NAD-binding pattern, TGXXGXXG, and active site tetrad. 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 1440590402  11 RRESLAVFGndypteDGTGVRDYIHVMDLADGHVAAMEKlADKAGVhiYNLGAGVGSSVLDVVNAFSKACGKPINYHFAP 90
Cdd:cd05230   195 RGEPITVYG------DGTQTRSFQYVSDLVEGLIRLMNS-DYFGGP--VNLGNPEEFTILELAELVKKLTGSKSEIVFLP 265

                          90       100       110
                  ....*....|....*....|....*....|....*...
gi 1440590402  91 RREGDLPAYWADAEKADRELNWRVTRNLDEMAQDTWHW 128
Cdd:cd05230   266 LPEDDPKRRRPDISKAKELLGWEPKVPLEEGLRRTIEY 303

GDP-4-keto-6-deoxymannose-3,5-epimerase-4-reductase

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1440590402  27 GTGVRDYIHVMDLADGHVAAMEKLADKagVHIyNLGAGVGSSVLDVVNAFSKACGKPINYHFAPRREGDLPAYWADAEKA 106
Cdd:PLN02725  199 GSPLREFLHVDDLADAVVFLMRRYSGA--EHV-NVGSGDEVTIKELAELVKEVVGFEGELVWDTSKPDGTPRKLMDSSKL 275

                          90       100
                  ....*....|....*....|..
gi 1440590402 107 dRELNWRVTRNLDEMAQDTWHW 128
Cdd:PLN02725  276 -RSLGWDPKFSLKDGLQETYKW 296

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 1440590402  30 VRDYIHVMDLADGHVAAMEKL-ADKAG-VHIYNLGAG--VGSSVLDVVNAFSKACGKpinyhfAPRREGDLP-----AYW 100
Cdd:cd05252   224 IRPWQHVLEPLSGYLLLAEKLyERGEEyAEAWNFGPDdeDAVTVLELVEAMARYWGE------DARWDLDGNshpheANL 297

                          90       100       110
                  ....*....|....*....|....*....|
gi 1440590402 101 A--DAEKADRELNWRVTRNLDEMAQDTWHW 128
Cdd:cd05252   298 LklDCSKAKTMLGWRPRWNLEETLEFTVAW 327