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 613309450   5 VLLAGGTGYIGKYL-SEVIENDAELFAISKYPDNKKTDDVE--MTWIQCDIFHYEQVVAAMNQIDIAVFFIDPTKNSAKI 81
Cdd:cd05245    1 VLVTGATGYVGGRLvPRLLQEGHQVRALVRSPEKLADRPWSerVTVVRGDLEDPESLRAALEGIDTAYYLVHSMGSGGDF 80

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 613309450  82 TQSSARdltliAADNFGRAAAINQVKKVIYIPG-------------SRydNETIERLGAYGTTVET 134
Cdd:cd05245   81 EEADRR-----AARNFARAARAAGVKRIIYLGGlipkgeelsphlrSR--AEVGEILRAGGVPVTE 139

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 613309450   5 VLLAGGTGYIGKYL-SEVIENDAELFAISKYPDNKKTDDVE--MTWIQCDIFHYEQVVAAMNQIDIAVFFIDPTKNSAKI 81
Cdd:cd05245    1 VLVTGATGYVGGRLvPRLLQEGHQVRALVRSPEKLADRPWSerVTVVRGDLEDPESLRAALEGIDTAYYLVHSMGSGGDF 80

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 613309450  82 TQSSARdltliAADNFGRAAAINQVKKVIYIPG-------------SRydNETIERLGAYGTTVET 134
Cdd:cd05245   81 EEADRR-----AARNFARAARAAGVKRIIYLGGlipkgeelsphlrSR--AEVGEILRAGGVPVTE 139

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 613309450    5 VLLAGGTGYIGKYLSEV-IENDAELFAISKYPDNKKTD-DVEMTWIQCDIFHYEQVVAAMNQIDI-AVFfidptkNSAKI 81
Cdd:pfam01370   1 ILVTGATGFIGSHLVRRlLEKGYEVIGLDRLTSASNTArLADLRFVEGDLTDRDALEKLLADVRPdAVI------HLAAV 74

                          90       100       110
                  ....*....|....*....|....*....|....*....
gi 613309450   82 T--QSSARDLTLIAADNFG------RAAAINQVKKVIYI 112
Cdd:pfam01370  75 GgvGASIEDPEDFIEANVLgtlnllEAARKAGVKRFLFA 113

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 613309450   5 VLLAGGTGYIGKYL-SEVIENDAELFAISKYPDNKKTDDVE--MTWIQCDIFHYEQVVAAMNQIDIAVFFIDPTKNSAKI 81
Cdd:cd05245    1 VLVTGATGYVGGRLvPRLLQEGHQVRALVRSPEKLADRPWSerVTVVRGDLEDPESLRAALEGIDTAYYLVHSMGSGGDF 80

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 613309450  82 TQSSARdltliAADNFGRAAAINQVKKVIYIPG-------------SRydNETIERLGAYGTTVET 134
Cdd:cd05245   81 EEADRR-----AARNFARAARAAGVKRIIYLGGlipkgeelsphlrSR--AEVGEILRAGGVPVTE 139

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 613309450   4 KVLLAGGTGYIGKYLSEV-IENDAELFAISKYPDNKKT--DDVEMTWIQCDIFHYEQVVAAMNQIDIAVFF---IDPTKN 77
Cdd:COG0451    1 RILVTGGAGFIGSHLARRlLARGHEVVGLDRSPPGAANlaALPGVEFVRGDLRDPEALAAALAGVDAVVHLaapAGVGEE 80

                         90       100       110
                 ....*....|....*....|....*....|....*
gi 613309450  78 SAKITQSSARDLTLiaadNFGRAAAINQVKKVIYI 112
Cdd:COG0451   81 DPDETLEVNVEGTL----NLLEAARAAGVKRFVYA 111

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 613309450    5 VLLAGGTGYIGKYLSEV-IENDAELFAISKYPDNKKTD-DVEMTWIQCDIFHYEQVVAAMNQIDI-AVFfidptkNSAKI 81
Cdd:pfam01370   1 ILVTGATGFIGSHLVRRlLEKGYEVIGLDRLTSASNTArLADLRFVEGDLTDRDALEKLLADVRPdAVI------HLAAV 74

                          90       100       110
                  ....*....|....*....|....*....|....*....
gi 613309450   82 T--QSSARDLTLIAADNFG------RAAAINQVKKVIYI 112
Cdd:pfam01370  75 GgvGASIEDPEDFIEANVLgtlnllEAARKAGVKRFLFA 113