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 74714590  53 RVLITGALGQLGVGLANLLRKRFGKDSVILSDIRKPPDHVFHSGPFIYSDILDYKNLREIVVNNRITWLFHYSALLSAFG 132
Cdd:cd05272   1 RILITGGLGQIGSELAKLLRKRYGKDNVIASDIRKPPAHVVLSGPFEYLDVLDFKSLEEIVVNHKITWIIHLAALLSAVG 80

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 74714590 133 EANVSLARAVNITGLHNILDVAAEHNLQLFVPSTIGAFGPTSPRNPTPDLCIQRPRTIYGVSKVHAELMGETMQSRF 209
Cdd:cd05272  81 EKNPPLAWDVNMNGLHNVLELAREHNLRIFVPSTIGAFGPTTPRNNTPDDTIQRPRTIYGVSKVAAELLGEYYHHKF 157

L-threonine dehydrogenase, extended (e) SDRs; This subgroup contains members identified as L-threonine dehydrogenase (TDH). TDH catalyzes the zinc-dependent formation of 2-amino-3-ketobutyrate from L-threonine via NAD(H)-dependent oxidation. This group is distinct from TDHs that are members of the medium chain dehydrogenase/reductase family. This group has the NAD-binding motif and active site tetrad 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 74714590  53 RVLITGALGQLGVGLANLLRKRFGKDSVILSDIRKPPDHVFHSGPFIYSDILDYKNLREIVVNNRITWLFHYSALLSAFG 132
Cdd:cd05272   1 RILITGGLGQIGSELAKLLRKRYGKDNVIASDIRKPPAHVVLSGPFEYLDVLDFKSLEEIVVNHKITWIIHLAALLSAVG 80

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 74714590 133 EANVSLARAVNITGLHNILDVAAEHNLQLFVPSTIGAFGPTSPRNPTPDLCIQRPRTIYGVSKVHAELMGETMQSRF 209
Cdd:cd05272  81 EKNPPLAWDVNMNGLHNVLELAREHNLRIFVPSTIGAFGPTTPRNNTPDDTIQRPRTIYGVSKVAAELLGEYYHHKF 157

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 74714590    54 VLITGALGQLGVGLANLLRKRFGKDSVILSDIRKPPDHVFHSGPFIYSDILDYKNLREIVVNNRITWLFHYSALlsAFGE 133
Cdd:pfam01370   1 ILVTGATGFIGSHLVRRLLEKGYEVIGLDRLTSASNTARLADLRFVEGDLTDRDALEKLLADVRPDAVIHLAAV--GGVG 78

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 74714590   134 ANVSLARA---VNITGLHNILDVAAEHNLQLFV-PSTIGAFGP--TSPRNPTPDLCIQRPRTIYGVSKVHAELM 201
Cdd:pfam01370  79 ASIEDPEDfieANVLGTLNLLEAARKAGVKRFLfASSSEVYGDgaEIPQEETTLTGPLAPNSPYAAAKLAGEWL 152

sugar epimerase family protein;

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 74714590   53 RVLITGALGQLGVGLANLLRKRfGKDSVILSdiRKPPDHVFHSGPFIYSDILDYKNLREIVVNNRITWLFHYSAllsafg 132
Cdd:PRK05865   2 RIAVTGASGVLGRGLTARLLSQ-GHEVVGIA--RHRPDSWPSSADFIAADIRDATAVESAMTGADVVAHCAWVR------ 72

                         90       100
                 ....*....|....*....|....
gi 74714590  133 eanvSLARAVNITGLHNILDVAAE 156
Cdd:PRK05865  73 ----GRNDHINIDGTANVLKAMAE 92

L-threonine dehydrogenase, extended (e) SDRs; This subgroup contains members identified as L-threonine dehydrogenase (TDH). TDH catalyzes the zinc-dependent formation of 2-amino-3-ketobutyrate from L-threonine via NAD(H)-dependent oxidation. This group is distinct from TDHs that are members of the medium chain dehydrogenase/reductase family. This group has the NAD-binding motif and active site tetrad 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 74714590  53 RVLITGALGQLGVGLANLLRKRFGKDSVILSDIRKPPDHVFHSGPFIYSDILDYKNLREIVVNNRITWLFHYSALLSAFG 132
Cdd:cd05272   1 RILITGGLGQIGSELAKLLRKRYGKDNVIASDIRKPPAHVVLSGPFEYLDVLDFKSLEEIVVNHKITWIIHLAALLSAVG 80

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 74714590 133 EANVSLARAVNITGLHNILDVAAEHNLQLFVPSTIGAFGPTSPRNPTPDLCIQRPRTIYGVSKVHAELMGETMQSRF 209
Cdd:cd05272  81 EKNPPLAWDVNMNGLHNVLELAREHNLRIFVPSTIGAFGPTTPRNNTPDDTIQRPRTIYGVSKVAAELLGEYYHHKF 157

Escherichia coli Gne (a nucleoside-diphosphate-sugar 4-epimerase)-like, extended (e) SDRs; Nucleoside-diphosphate-sugar 4-epimerase has the characteristic active site tetrad and NAD-binding motif of the extended SDR, and is related to more specifically defined epimerases such as UDP-glucose 4 epimerase (aka UDP-galactose-4-epimerase), which catalyzes the NAD-dependent conversion of UDP-galactose to UDP-glucose, the final step in Leloir galactose synthesis. This subgroup includes Escherichia coli 055:H7 Gne, a UDP-GlcNAc 4-epimerase, essential for O55 antigen 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 74714590  52 PRVLITGALGQLGVGLANLLRKRFGKDSVILSDIRKPPDHVFHSGPFIYSDILDYKNLREIVVNNRITWLFHYSALLSAF 131
Cdd:cd05238   1 MKVLITGASGFVGQRLAERLLSDVPNERLILIDVVSPKAPSGAPRVTQIAGDLAVPALIEALANGRPDVVFHLAAIVSGG 80

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 74714590 132 GEANVSLARAVNITGLHNILDVAAEHN--LQLFVPSTIGAFGPTSPrNPTPDLCIQRPRTIYGVSKVHAELM 201
Cdd:cd05238  81 AEADFDLGYRVNVDGTRNLLEALRKNGpkPRFVFTSSLAVYGLPLP-NPVTDHTALDPASSYGAQKAMCELL 151

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 74714590  54 VLITGALGQLGVGLANLLRKRFGKdsVILSDIRkppDHVFHSGpfiysdildyknlreivvnnritwlfhysALLS-AFG 132
Cdd:cd08946   1 ILVTGGAGFIGSHLVRRLLERGHE--VVVIDRL---DVVVHLA-----------------------------ALVGvPAS 46

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 74714590 133 EANVSLARAVNITGLHNILDVAAEHNLQLFV-PSTIGAFGPTSPrNPTPDLCIQRPRTIYGVSKVHAELMGETMQSRFSM 211
Cdd:cd08946  47 WDNPDEDFETNVVGTLNLLEAARKAGVKRFVyASSASVYGSPEG-LPEEEETPPRPLSPYGVSKLAAEHLLRSYGESYGL 125

dTDP-4-dehydrorhamnose reductase [Cell wall/membrane/envelope biogenesis];

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 74714590  53 RVLITGALGQLGVGLANLLRKRFGkdSVILSDIRKppdhvfhsgpfiySDILDYKNLREIVVNNRITWLFH---YSALLS 129
Cdd:COG1091   1 RILVTGANGQLGRALVRLLAERGY--EVVALDRSE-------------LDITDPEAVAALLEEVRPDVVINaaaYTAVDK 65

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 74714590 130 AfgEANVSLARAVNITGLHNILDVAAEHNLQLFVPST--------IGAFGPTSPRNPTpdlciqrprTIYGVSKvhaeLM 201
Cdd:COG1091  66 A--ESEPELAYAVNATGPANLAEACAELGARLIHISTdyvfdgtkGTPYTEDDPPNPL---------NVYGRSK----LA 130

                ..
gi 74714590 202 GE 203
Cdd:COG1091 131 GE 132

dTDP-6-deoxy-L-lyxo-4-hexulose reductase and related proteins, extended (e) SDRs; dTDP-6-deoxy-L-lyxo-4-hexulose reductase, an extended SDR, synthesizes dTDP-L-rhamnose from alpha-D-glucose-1-phosphate, providing the precursor of L-rhamnose, an essential cell wall component of many pathogenic bacteria. This subgroup has the characteristic active site tetrad and NADP-binding motif. This subgroup also contains human MAT2B, the regulatory subunit of methionine adenosyltransferase (MAT); MAT catalyzes S-adenosylmethionine synthesis. The human gene encoding MAT2B encodes two major splicing variants which are induced in human cell liver cancer and regulate HuR, an mRNA-binding protein which stabilizes the mRNA of several cyclins, to affect cell proliferation. Both MAT2B variants include this extended SDR domain. 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 74714590  53 RVLITGALGQLGVGLANLLRKRfGKDSVILSDIRKPPDHVfhsgpfiysDILDYKNLREIVVNNRITWLFH---YSALLS 129
Cdd:cd05254   1 KILITGATGMLGRALVRLLKER-GYEVIGTGRSRASLFKL---------DLTDPDAVEEAIRDYKPDVIINcaaYTRVDK 70

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 74714590 130 AfgEANVSLARAVNITGLHNILDVAAEHNLQLFVPSTIGAF-GPTSPRNPTpDLCIqrPRTIYGVSKVHAEL 200
Cdd:cd05254  71 C--ESDPELAYRVNVLAPENLARAAKEVGARLIHISTDYVFdGKKGPYKEE-DAPN--PLNVYGKSKLLGEV 137

UDP-N-acetylglucosamine 4-epimerase, extended (e) SDRs; This subgroup contains UDP-N-acetylglucosamine 4-epimerase of Pseudomonas aeruginosa, WbpP, an extended SDR, that catalyzes the NAD+ dependent conversion of UDP-GlcNAc and UDPGalNA to UDP-Glc and UDP-Gal. 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 74714590  53 RVLITGALGQLGVGLANLLRKRfGKDSVILSD--------IRKPPDHVfhsgPFIYSDILDYKNLREIVvnNRITWLFHy 124
Cdd:cd05256   1 RVLVTGGAGFIGSHLVERLLER-GHEVIVLDNlstgkkenLPEVKPNV----KFIEGDIRDDELVEFAF--EGVDYVFH- 72

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 74714590 125 salLSAFGEANVSLAR-----AVNITGLHNILDVAAEHNLQLFV-PSTIGAFGPtSPRNPTPDLCIQRPRTIYGVSKVHA 198
Cdd:cd05256  73 ---QAAQASVPRSIEDpikdhEVNVLGTLNLLEAARKAGVKRFVyASSSSVYGD-PPYLPKDEDHPPNPLSPYAVSKYAG 148

                ..
gi 74714590 199 EL 200
Cdd:cd05256 149 EL 150

3beta-hydroxysteroid dehydrogenase (3b-HSD)-like, subgroup1, extended (e) SDRs; An uncharacterized subgroup of the 3b-HSD-like extended-SDR family. Proteins in this subgroup have the characteristic active site tetrad and NAD(P)-binding motif of extended-SDRs. 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. 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 74714590  54 VLITGALGQLGVGLANLLRKRfgKDSVILSDIRKPPDHVFHSGPFIYSDILDYKNLREIVVNnrITWLFHYSAL-LSAFG 132
Cdd:cd09812   2 VLITGGGGYFGFRLGCALAKS--GVHVILFDIRRPQQELPEGIKFIQADVRDLSQLEKAVAG--VDCVFHIASYgMSGRE 77

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*..
gi 74714590 133 EANVSLARAVNITGLHNILDVAAEHNL-QLFVPSTIG-AFGPTSPRN 177
Cdd:cd09812  78 QLNRELIEEINVRGTENIIQVCVRRRVpRLIYTSTFNvIFGGQPIRN 124

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 74714590  53 RVLITGALGQLGVGLANLLRKRfgKDSVIL---SDIRKPPDHVFHSGPfiysDIlDYKNLREivvnNRITWLFHYSALLS 129
Cdd:cd05232   1 KVLVTGANGFIGRALVDKLLSR--GEEVRIavrNAENAEPSVVLAELP----DI-DSFTDLF----LGVDAVVHLAARVH 69

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 74714590 130 AF---GEANVSLARAVNITGLHNILDVAAEHNLQLFV-PSTIGAFGPTSPRNPTPDLCIQRPRTIYGVSKVHAELMGETM 205
Cdd:cd05232  70 VMndqGADPLSDYRKVNTELTRRLARAAARQGVKRFVfLSSVKVNGEGTVGAPFDETDPPAPQDAYGRSKLEAERALLEL 149

                ....*.
gi 74714590 206 QSRFSM 211
Cdd:cd05232 150 GASDGM 155

dTDP-D-glucose 4,6-dehydratase, extended (e) SDRs; This subgroup contains dTDP-D-glucose 4,6-dehydratase and related proteins, members of the extended-SDR family, with the characteristic Rossmann fold core region, active site tetrad and NAD(P)-binding motif. dTDP-D-glucose 4,6-dehydratase is closely related to other sugar epimerases of the SDR family. dTDP-D-dlucose 4,6,-dehydratase catalyzes the second of four steps in the dTDP-L-rhamnose pathway (the dehydration of dTDP-D-glucose to dTDP-4-keto-6-deoxy-D-glucose) in the synthesis of L-rhamnose, a cell wall component of some pathogenic bacteria. In many gram negative bacteria, L-rhamnose is an important constituent of lipopoylsaccharide O-antigen. The larger N-terminal portion of dTDP-D-Glucose 4,6-dehydratase forms a Rossmann fold NAD-binding domain, while the C-terminus binds the sugar substrate. 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 74714590  53 RVLITGALGQLGVGLANLLRKRFGKDSVI-------------LSDIRKPPDHvfhsgPFIYSDILDYKNLREIVVNNRIT 119
Cdd:cd05246   2 KILVTGGAGFIGSNFVRYLLNKYPDYKIInldkltyagnlenLEDVSSSPRY-----RFVKGDICDAELVDRLFEEEKID 76

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 74714590 120 WLFHYSAllsafgEANV--SLARA-----VNITGLHNILDVAAEHNLQLFVP-ST---------IGAFGPTSPRNPT-Pd 181
Cdd:cd05246  77 AVIHFAA------ESHVdrSISDPepfirTNVLGTYTLLEAARKYGVKRFVHiSTdevygdlldDGEFTETSPLAPTsP- 149

                       170       180
                ....*....|....*....|
gi 74714590 182 lciqrprtiYGVSKVHAELM 201
Cdd:cd05246 150 ---------YSASKAAADLL 160

UDP-Glcnac (UDP-linked N-acetylglucosamine) inverting 4,6-dehydratase, extended (e) SDRs; UDP-Glcnac inverting 4,6-dehydratase was identified in Helicobacter pylori as the hexameric flaA1 gene product (FlaA1). FlaA1 is hexameric, possesses UDP-GlcNAc-inverting 4,6-dehydratase activity, and catalyzes the first step in the creation of a pseudaminic acid derivative in protein glycosylation. Although this subgroup has the NADP-binding motif characteristic of extended SDRs, its members tend to have a Met substituted for the active site Tyr found in most SDR families. 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 74714590  53 RVLITGALGQLGVGLANLLrKRFGKDSVILSDI---------RKPPDHVFHS--GPFIySDILDYKNLREIVVNNRITWL 121
Cdd:cd05237   4 TILVTGGAGSIGSELVRQI-LKFGPKKLIVFDRdenklhelvRELRSRFPHDklRFII-GDVRDKERLRRAFKERGPDIV 81

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 74714590 122 FHYSALL---SAfgEANVSLARAVNITGLHNILDVAAEHNLQLFVP-STIGAfgptspRNPTpdlciqrprTIYGVSKVH 197
Cdd:cd05237  82 FHAAALKhvpSM--EDNPEEAIKTNVLGTKNVIDAAIENGVEKFVCiSTDKA------VNPV---------NVMGATKRV 144

                       170
                ....*....|....*....
gi 74714590 198 AELM-----GETMQSRFSM 211
Cdd:cd05237 145 AEKLllaknEYSSSTKFST 163

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 74714590  53 RVLITGALGQLGVGLANLLRKRFgkDSVILSDIRKPPDHVFHSG-PFIYSDILDYKNLREIVVNNRItwLFHY-SALLSA 130
Cdd:cd05264   1 RVLIVGGNGFIGSHLVDALLEEG--PQVRVFDRSIPPYELPLGGvDYIKGDYENRADLESALVGIDT--VIHLaSTTNPA 76

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 74714590 131 FGEANVSLARAVNITGLHNILDVAAEHNLQ-LFVPSTIGA-FG-----PTSPRNPTpdlciqRPRTIYGVSKVHAELMGE 203
Cdd:cd05264  77 TSNKNPILDIQTNVAPTVQLLEACAAAGIGkIIFASSGGTvYGvpeqlPISESDPT------LPISSYGISKLAIEKYLR 150

                ....*
gi 74714590 204 TMQSR 208
Cdd:cd05264 151 LYQYL 155

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 74714590  53 RVLITGALGQLGVGLANLLRKRFGKDSVI--LSDIRKPPDHVFHSGPFIYSDILDYKNLREIVVNNRITWLFHYSAllSA 130
Cdd:cd05234   1 RILVTGGAGFIGSHLVDRLLEEGNEVVVVdnLSSGRRENIEPEFENKAFRFVKRDLLDTADKVAKKDGDTVFHLAA--NP 78

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 74714590 131 ---FGEANVSLARAVNITGLHNILDVAAEHNLQLFVPSTIGAFGPTSPRNPTPDLCIQRPRTIYGVSKVHAELM 201
Cdd:cd05234  79 dvrLGATDPDIDLEENVLATYNVLEAMRANGVKRIVFASSSTVYGEAKVIPTPEDYPPLPISVYGASKLAAEAL 152

sugar epimerase family protein;

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 74714590   53 RVLITGALGQLGVGLANLLRKRfGKDSVILSdiRKPPDHVFHSGPFIYSDILDYKNLREIVVNNRITWLFHYSAllsafg 132
Cdd:PRK05865   2 RIAVTGASGVLGRGLTARLLSQ-GHEVVGIA--RHRPDSWPSSADFIAADIRDATAVESAMTGADVVAHCAWVR------ 72

                         90       100
                 ....*....|....*....|....
gi 74714590  133 eanvSLARAVNITGLHNILDVAAE 156
Cdd:PRK05865  73 ----GRNDHINIDGTANVLKAMAE 92

Polysaccharide biosynthesis protein; This is a family of diverse bacterial polysaccharide biosynthesis proteins including the CapD protein, WalL protein mannosyl-transferase and several putative epimerases (e.g. WbiI).

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 74714590    54 VLITGALGQLGVGLAN-LLRKR------FGKDSVILSDIRK-----PPDH--VFHSGPFIySDILDYKNLREIVVNNRIT 119
Cdd:pfam02719   1 VLVTGGGGSIGSELCRqILKFNpkkiilFSRDELKLYEIRQelrekFNDPklRFFIVPVI-GDVRDRERLERAMEQYGVD 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 74714590   120 WLFHYSAL----LsafGEANVSLARAVNITGLHNILDVAAEHNLQLFVP-STIGAFGPTSprnptpdlciqrprtIYGVS 194
Cdd:pfam02719  80 VVFHAAAYkhvpL---VEYNPMEAIKTNVLGTENVADAAIEAGVKKFVLiSTDKAVNPTN---------------VMGAT 141

                         170       180
                  ....*....|....*....|....
gi 74714590   195 KVHAELM-------GETMQSRFSM 211
Cdd:pfam02719 142 KRLAEKLfqaanreSGSGGTRFSV 165

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 74714590  53 RVLITGALGQLGVGLANLLRKRFGKDSVI--LSDIRK---PPDHVFHSGPFIYSDILDYKNLREIVVNNRITwlFHYSAL 127
Cdd:cd05257   1 NVLVTGADGFIGSHLTERLLREGHEVRALdiYNSFNSwglLDNAVHDRFHFISGDVRDASEVEYLVKKCDVV--FHLAAL 78

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 74714590 128 LsAFGEANVSLARAV--NITGLHNILDVAAEHNLQLFV-PSTIGAFGPTSP---RNPTPDLCIQRPRTIYGVSKVHAELM 201
Cdd:cd05257  79 I-AIPYSYTAPLSYVetNVFGTLNVLEAACVLYRKRVVhTSTSEVYGTAQDvpiDEDHPLLYINKPRSPYSASKQGADRL 157

                ..
gi 74714590 202 GE 203
Cdd:cd05257 158 AY 159