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 568966264  30 KYVFITGCDSGFGNLLARQLDRRGMRVLAACLTE--KGAEELRNKTSDRLETVILDVTKTESIVAATQWVKERVGNRGLW 107
Cdd:cd09805    1 KAVLITGCDSGFGNLLAKKLDSLGFTVLAGCLTKngPGAKELRRVCSDRLRTLQLDVTKPEQIKRAAQWVKEHVGEKGLW 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568966264 108 GLVNNAGISTPSGPNEWMKKQDFARVLDVNLLGMIEVTLSMLPLVRKARGRVVNVSSVMGRMSFF-GGGYCISKYGVEAF 186
Cdd:cd09805   81 GLVNNAGILGFGGDEELLPMDDYRKCMEVNLFGTVEVTKAFLPLLRRAKGRVVNVSSMGGRVPFPaGGAYCASKAAVEAF 160

                 ....*..
gi 568966264 187 SDSLRSE 193
Cdd:cd09805  161 SDSLRRE 167

human 17beta-hydroxysteroid dehydrogenase type 2 (type 2 17beta-HSD)-like, classical (c) SDRs; 17beta-hydroxysteroid dehydrogenases are a group of isozymes that catalyze activation and inactivation of estrogen and androgens. This classical-SDR subgroup includes the human proteins: type 2 17beta-HSD, type 6 17beta-HSD, type 2 11beta-HSD, dehydrogenase/reductase SDR family member 9, short-chain dehydrogenase/reductase family 9C member 7, 3-hydroxybutyrate dehydrogenase type 1, and retinol dehydrogenase 5. SDRs are a functionally diverse family of oxidoreductases that have a single domain with a structurally conserved Rossmann fold (alpha/beta folding pattern with a central beta-sheet), an NAD(P)(H)-binding region, and a structurally diverse C-terminal region. Classical SDRs are typically about 250 residues long, while extended SDRs are approximately 350 residues. Sequence identity between different SDR enzymes are typically in the 15-30% range, but the enzymes share the Rossmann fold NAD-binding motif and characteristic NAD-binding and catalytic sequence patterns. These enzymes 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 (15-PGDH) numbering). In addition to the Tyr and Lys, there is often an upstream Ser (Ser-138, 15-PGDH numbering) and/or an Asn (Asn-107, 15-PGDH numbering) 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. Extended SDRs have additional elements in the C-terminal region, 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. Some atypical SDRs have lost catalytic activity and/or have an unusual NAD(P)-binding motif and missing or unusual active site residues. Reactions catalyzed within the SDR family include isomerization, decarboxylation, epimerization, C=N bond reduction, dehydratase activity, dehalogenation, Enoyl-CoA reduction, and carbonyl-alcohol oxidoreduction.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568966264  30 KYVFITGCDSGFGNLLARQLDRRGMRVLAACLTE--KGAEELRNKTSDRLETVILDVTKTESIVAATQWVKERVGNRGLW 107
Cdd:cd09805    1 KAVLITGCDSGFGNLLAKKLDSLGFTVLAGCLTKngPGAKELRRVCSDRLRTLQLDVTKPEQIKRAAQWVKEHVGEKGLW 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568966264 108 GLVNNAGISTPSGPNEWMKKQDFARVLDVNLLGMIEVTLSMLPLVRKARGRVVNVSSVMGRMSFF-GGGYCISKYGVEAF 186
Cdd:cd09805   81 GLVNNAGILGFGGDEELLPMDDYRKCMEVNLFGTVEVTKAFLPLLRRAKGRVVNVSSMGGRVPFPaGGAYCASKAAVEAF 160

                 ....*..
gi 568966264 187 SDSLRSE 193
Cdd:cd09805  161 SDSLRRE 167

short chain dehydrogenase; This family contains a wide variety of dehydrogenases.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568966264   30 KYVFITGCDSGFGNLLARQLDRRGMRVLAACLT----EKGAEELRNkTSDRLETVILDVTKTESIVAATQWVKERVGnrG 105
Cdd:pfam00106   1 KVALVTGASSGIGRAIAKRLAKEGAKVVLVDRSeeklEAVAKELGA-LGGKALFIQGDVTDRAQVKALVEQAVERLG--R 77

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568966264  106 LWGLVNNAGIsTPSGPNEWMKKQDFARVLDVNLLGMIEVTLSMLP-LVRKARGRVVNVSSVMGRMSFFGGG-YCISKYGV 183
Cdd:pfam00106  78 LDILVNNAGI-TGLGPFSELSDEDWERVIDVNLTGVFNLTRAVLPaMIKGSGGRIVNISSVAGLVPYPGGSaYSASKAAV 156

                         170
                  ....*....|....*.
gi 568966264  184 EAFSDSLRSE-KPKRI 198
Cdd:pfam00106 157 IGFTRSLALElAPHGI 172

3-oxoacyl-(acyl-carrier-protein) reductase; This model represents 3-oxoacyl-[ACP] reductase, also called 3-ketoacyl-acyl carrier protein reductase, an enzyme of fatty acid biosynthesis. [Fatty acid and phospholipid metabolism, Biosynthesis]

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568966264   32 VFITGCDSGFGNLLARQLDRRGMRVLAACLT-EKGAEELRNKTSD---RLETVILDVTKTESIVAATQWVKERVGnrGLW 107
Cdd:TIGR01830   1 ALVTGASRGIGRAIALKLAKEGAKVIITYRSsEEGAEEVVEELKAlgvKALGVVLDVSDREDVKAVVEEIEEELG--TID 78

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568966264  108 GLVNNAGIsTPSGPNEWMKKQDFARVLDVNLLGMIEVTLSMLPLVRKAR-GRVVNVSSVMGRMSFFG-GGYCISKYGVEA 185
Cdd:TIGR01830  79 ILVNNAGI-TRDNLLMRMKEEDWDAVIDTNLTGVFNLTQAVLRIMIKQRsGRIINISSVVGLMGNAGqANYAASKAGVIG 157

                  ....*...
gi 568966264  186 FSDSLRSE 193
Cdd:TIGR01830 158 FTKSLAKE 165

human 17beta-hydroxysteroid dehydrogenase type 2 (type 2 17beta-HSD)-like, classical (c) SDRs; 17beta-hydroxysteroid dehydrogenases are a group of isozymes that catalyze activation and inactivation of estrogen and androgens. This classical-SDR subgroup includes the human proteins: type 2 17beta-HSD, type 6 17beta-HSD, type 2 11beta-HSD, dehydrogenase/reductase SDR family member 9, short-chain dehydrogenase/reductase family 9C member 7, 3-hydroxybutyrate dehydrogenase type 1, and retinol dehydrogenase 5. SDRs are a functionally diverse family of oxidoreductases that have a single domain with a structurally conserved Rossmann fold (alpha/beta folding pattern with a central beta-sheet), an NAD(P)(H)-binding region, and a structurally diverse C-terminal region. Classical SDRs are typically about 250 residues long, while extended SDRs are approximately 350 residues. Sequence identity between different SDR enzymes are typically in the 15-30% range, but the enzymes share the Rossmann fold NAD-binding motif and characteristic NAD-binding and catalytic sequence patterns. These enzymes 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 (15-PGDH) numbering). In addition to the Tyr and Lys, there is often an upstream Ser (Ser-138, 15-PGDH numbering) and/or an Asn (Asn-107, 15-PGDH numbering) 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. Extended SDRs have additional elements in the C-terminal region, 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. Some atypical SDRs have lost catalytic activity and/or have an unusual NAD(P)-binding motif and missing or unusual active site residues. Reactions catalyzed within the SDR family include isomerization, decarboxylation, epimerization, C=N bond reduction, dehydratase activity, dehalogenation, Enoyl-CoA reduction, and carbonyl-alcohol oxidoreduction.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568966264  30 KYVFITGCDSGFGNLLARQLDRRGMRVLAACLTE--KGAEELRNKTSDRLETVILDVTKTESIVAATQWVKERVGNRGLW 107
Cdd:cd09805    1 KAVLITGCDSGFGNLLAKKLDSLGFTVLAGCLTKngPGAKELRRVCSDRLRTLQLDVTKPEQIKRAAQWVKEHVGEKGLW 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568966264 108 GLVNNAGISTPSGPNEWMKKQDFARVLDVNLLGMIEVTLSMLPLVRKARGRVVNVSSVMGRMSFF-GGGYCISKYGVEAF 186
Cdd:cd09805   81 GLVNNAGILGFGGDEELLPMDDYRKCMEVNLFGTVEVTKAFLPLLRRAKGRVVNVSSMGGRVPFPaGGAYCASKAAVEAF 160

                 ....*..
gi 568966264 187 SDSLRSE 193
Cdd:cd09805  161 SDSLRRE 167

Short-chain dehydrogenase [General function prediction only];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568966264  27 LQDKYVFITGCDSGFGNLLARQLDRRGMRVLAACLTEKGAEELRN---KTSDRLETVILDVTKTESIVAATQWVKERVGn 103
Cdd:COG0300    3 LTGKTVLITGASSGIGRALARALAARGARVVLVARDAERLEALAAelrAAGARVEVVALDVTDPDAVAALAEAVLARFG- 81

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568966264 104 rGLWGLVNNAGISTPsGPNEWMKKQDFARVLDVNLLGMIEVTLSMLP-LVRKARGRVVNVSSVMGRMSF-FGGGYCISKY 181
Cdd:COG0300   82 -PIDVLVNNAGVGGG-GPFEELDLEDLRRVFEVNVFGPVRLTRALLPlMRARGRGRIVNVSSVAGLRGLpGMAAYAASKA 159

                        170
                 ....*....|..
gi 568966264 182 GVEAFSDSLRSE 193
Cdd:COG0300  160 ALEGFSESLRAE 171

short chain dehydrogenase; This family contains a wide variety of dehydrogenases.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568966264   30 KYVFITGCDSGFGNLLARQLDRRGMRVLAACLT----EKGAEELRNkTSDRLETVILDVTKTESIVAATQWVKERVGnrG 105
Cdd:pfam00106   1 KVALVTGASSGIGRAIAKRLAKEGAKVVLVDRSeeklEAVAKELGA-LGGKALFIQGDVTDRAQVKALVEQAVERLG--R 77

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568966264  106 LWGLVNNAGIsTPSGPNEWMKKQDFARVLDVNLLGMIEVTLSMLP-LVRKARGRVVNVSSVMGRMSFFGGG-YCISKYGV 183
Cdd:pfam00106  78 LDILVNNAGI-TGLGPFSELSDEDWERVIDVNLTGVFNLTRAVLPaMIKGSGGRIVNISSVAGLVPYPGGSaYSASKAAV 156

                         170
                  ....*....|....*.
gi 568966264  184 EAFSDSLRSE-KPKRI 198
Cdd:pfam00106 157 IGFTRSLALElAPHGI 172

classical (c) SDRs; SDRs are a functionally diverse family of oxidoreductases that have a single domain with a structurally conserved Rossmann fold (alpha/beta folding pattern with a central beta-sheet), an NAD(P)(H)-binding region, and a structurally diverse C-terminal region. Classical SDRs are typically about 250 residues long, while extended SDRs are approximately 350 residues. Sequence identity between different SDR enzymes are typically in the 15-30% range, but the enzymes share the Rossmann fold NAD-binding motif and characteristic NAD-binding and catalytic sequence patterns. These enzymes 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 prostaglandin dehydrogenase (PGDH) numbering). In addition to the Tyr and Lys, there is often an upstream Ser (Ser-138, PGDH numbering) and/or an Asn (Asn-107, PGDH numbering) 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. Extended SDRs have additional elements in the C-terminal region, 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. Some atypical SDRs have lost catalytic activity and/or have an unusual NAD(P)-binding motif and missing or unusual active site residues. Reactions catalyzed within the SDR family include isomerization, decarboxylation, epimerization, C=N bond reduction, dehydratase activity, dehalogenation, Enoyl-CoA reduction, and carbonyl-alcohol oxidoreduction.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568966264  32 VFITGCDSGFGNLLARQLDRRGMRVLAACLTEKGAEELRNKTSD--RLETVILDVTKTESIVAATQWVKERVGnrGLWGL 109
Cdd:cd05233    1 ALVTGASSGIGRAIARRLAREGAKVVLADRNEEALAELAAIEALggNAVAVQADVSDEEDVEALVEEALEEFG--RLDIL 78

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568966264 110 VNNAGISTPsGPNEWMKKQDFARVLDVNLLGMIEVTLSMLPLVRKAR-GRVVNVSSVMGRMSFFG-GGYCISKYGVEAFS 187
Cdd:cd05233   79 VNNAGIARP-GPLEELTDEDWDRVLDVNLTGVFLLTRAALPHMKKQGgGRIVNISSVAGLRPLPGqAAYAASKAALEGLT 157

                 ....*.
gi 568966264 188 DSLRSE 193
Cdd:cd05233  158 RSLALE 163

11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1)-like, classical (c) SDRs; Human 11beta_HSD1 catalyzes the NADP(H)-dependent interconversion of cortisone and cortisol. This subgroup also includes human dehydrogenase/reductase SDR family member 7C (DHRS7C) and DHRS7B. These proteins have the GxxxGxG nucleotide binding motif and S-Y-K catalytic triad characteristic of the SDRs, but have an atypical C-terminal domain that contributes to homodimerization contacts. SDRs are a functionally diverse family of oxidoreductases that have a single domain with a structurally conserved Rossmann fold (alpha/beta folding pattern with a central beta-sheet), an NAD(P)(H)-binding region, and a structurally diverse C-terminal region. Classical SDRs are typically about 250 residues long, while extended SDRs are approximately 350 residues. Sequence identity between different SDR enzymes are typically in the 15-30% range, but the enzymes share the Rossmann fold NAD-binding motif and characteristic NAD-binding and catalytic sequence patterns. These enzymes 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 (15-PGDH) numbering). In addition to the Tyr and Lys, there is often an upstream Ser (Ser-138, 15-PGDH numbering) and/or an Asn (Asn-107, 15-PGDH numbering) 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. Extended SDRs have additional elements in the C-terminal region, 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. Some atypical SDRs have lost catalytic activity and/or have an unusual NAD(P)-binding motif and missing or unusual active site residues. Reactions catalyzed within the SDR family include isomerization, decarboxylation, epimerization, C=N bond reduction, dehydratase activity, dehalogenation, Enoyl-CoA reduction, and carbonyl-alcohol oxidoreduction.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568966264  27 LQDKYVFITGCDSGFGNLLARQLDRRGMRVLaacLT-------EKGAEELRNKTSDRLETVILDVTKTESIVAATQWVKE 99
Cdd:cd05332    1 LQGKVVIITGASSGIGEELAYHLARLGARLV---LSarreerlEEVKSECLELGAPSPHVVPLDMSDLEDAEQVVEEALK 77

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568966264 100 RVGnrGLWGLVNNAGISTPSgpnEWMKK--QDFARVLDVNLLGMIEVTLSMLP-LVRKARGRVVNVSSVMGRMSF-FGGG 175
Cdd:cd05332   78 LFG--GLDILINNAGISMRS---LFHDTsiDVDRKIMEVNYFGPVALTKAALPhLIERSQGSIVVVSSIAGKIGVpFRTA 152

                        170
                 ....*....|....*...
gi 568966264 176 YCISKYGVEAFSDSLRSE 193
Cdd:cd05332  153 YAASKHALQGFFDSLRAE 170

carbonyl reductase sniffer-like, classical (c) SDRs; Sniffer is an NADPH-dependent carbonyl reductase of the classical SDR family. Studies in Drosophila melanogaster implicate Sniffer in the prevention of neurodegeneration due to aging and oxidative-stress. This subgroup also includes Rhodococcus sp. AD45 IsoH, which is an NAD-dependent 1-hydroxy-2-glutathionyl-2-methyl-3-butene dehydrogenase involved in isoprene metabolism, Aspergillus nidulans StcE encoded by a gene which is part of a proposed sterigmatocystin biosynthesis gene cluster, Bacillus circulans SANK 72073 BtrF encoded by a gene found in the butirosin biosynthesis gene cluster, and Aspergillus parasiticus nor-1 involved in the biosynthesis of aflatoxins. SDRs are a functionally diverse family of oxidoreductases that have a single domain with a structurally conserved Rossmann fold (alpha/beta folding pattern with a central beta-sheet), an NAD(P)(H)-binding region, and a structurally diverse C-terminal region. Classical SDRs are typically about 250 residues long, while extended SDRs are approximately 350 residues. Sequence identity between different SDR enzymes are typically in the 15-30% range, but the enzymes share the Rossmann fold NAD-binding motif and characteristic NAD-binding and catalytic sequence patterns. These enzymes 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 (15-PGDH) numbering). In addition to the Tyr and Lys, there is often an upstream Ser (Ser-138, 15-PGDH numbering) and/or an Asn (Asn-107, 15-PGDH numbering) 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. Extended SDRs have additional elements in the C-terminal region, 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. Some atypical SDRs have lost catalytic activity and/or have an unusual NAD(P)-binding motif and missing or unusual active site residues. Reactions catalyzed within the SDR family include isomerization, decarboxylation, epimerization, C=N bond reduction, dehydratase activity, dehalogenation, Enoyl-CoA reduction, and carbonyl-alcohol oxidoreduction.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568966264  32 VFITGCDSGFGNLLARQLDRRG-MRVLAACLTEKGAEELRNKTSDRLETVILDVTKTESIVAATQWVKERVGNRGLWGLV 110
Cdd:cd05325    1 VLITGASRGIGLELVRQLLARGnNTVIATCRDPSAATELAALGASHSRLHILELDVTDEIAESAEAVAERLGDAGLDVLI 80

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 568966264 111 NNAGISTPSGPNEWMKKQDFARVLDVNLLGMIEVTLSMLPLVRKA-RGRVVNVSSVMGRMSFFGGG----YCISK 180
Cdd:cd05325   81 NNAGILHSYGPASEVDSEDLLEVFQVNVLGPLLLTQAFLPLLLKGaRAKIINISSRVGSIGDNTSGgwysYRASK 155

SDR family oxidoreductase;

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568966264  30 KYVFITGCDSGFGNLLARQLDRRGMRVLAACLTEKGAEELRNKT-----SDRLETVILDVTKTESIVAATQWVKErVGNR 104
Cdd:PRK06914   4 KIAIVTGASSGFGLLTTLELAKKGYLVIATMRNPEKQENLLSQAtqlnlQQNIKVQQLDVTDQNSIHNFQLVLKE-IGRI 82

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568966264 105 GLwgLVNNAGISTpSGPNEWMKKQDFARVLDVNLLGMIEVTLSMLPLVRKAR-GRVVNVSSVMGRMSFFG-GGYCISKYG 182
Cdd:PRK06914  83 DL--LVNNAGYAN-GGFVEEIPVEEYRKQFETNVFGAISVTQAVLPYMRKQKsGKIINISSISGRVGFPGlSPYVSSKYA 159

                        170
                 ....*....|.
gi 568966264 183 VEAFSDSLRSE 193
Cdd:PRK06914 160 LEGFSESLRLE 170

3-oxoacyl-ACP reductase FabG;

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568966264  27 LQDKYVFITGCDSGFGNLLARQLDRRGMRVLAACLTEKGAEELRNKTS---DRLETVILDVTKTESIVAATQWVKERVGn 103
Cdd:PRK05653   3 LQGKTALVTGASRGIGRAIALRLAADGAKVVIYDSNEEAAEALAAELRaagGEARVLVFDVSDEAAVRALIEAAVEAFG- 81

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568966264 104 rGLWGLVNNAGIsTPSGPNEWMKKQDFARVLDVNLLGMIEVTLSMLPLVRKAR-GRVVNVSSVMGRMSFFGGG-YCISKY 181
Cdd:PRK05653  82 -ALDILVNNAGI-TRDALLPRMSEEDWDRVIDVNLTGTFNVVRAALPPMIKARyGRIVNISSVSGVTGNPGQTnYSAAKA 159

                        170
                 ....*....|....*...
gi 568966264 182 GVEAFSDSLRSE-KPKRI 198
Cdd:PRK05653 160 GVIGFTKALALElASRGI 177

3-oxoacyl-ACP reductase;

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568966264  30 KYVFITGCDSGFGNLLARQLDRRGMRVLAACLTEKGA----EELRNKTSDRLETVILDVTKTESIVAATQWVKERVGNRG 105
Cdd:PRK12824   3 KIALVTGAKRGIGSAIARELLNDGYRVIATYFSGNDCakdwFEEYGFTEDQVRLKELDVTDTEECAEALAEIEEEEGPVD 82

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568966264 106 LwgLVNNAGISTPSGPNEwMKKQDFARVLDVNLLGMIEVTLSMLPLVR-KARGRVVNVSSVMGRMSFFGG-GYCISKYGV 183
Cdd:PRK12824  83 I--LVNNAGITRDSVFKR-MSHQEWNDVINTNLNSVFNVTQPLFAAMCeQGYGRIINISSVNGLKGQFGQtNYSAAKAGM 159

                        170
                 ....*....|
gi 568966264 184 EAFSDSLRSE 193
Cdd:PRK12824 160 IGFTKALASE 169

classical (c) SDR, subgroup 7; These proteins are members of the classical SDR family, with a canonical active site triad (and also an active site Asn) and a typical Gly-rich NAD-binding motif. SDRs are a functionally diverse family of oxidoreductases that have a single domain with a structurally conserved Rossmann fold (alpha/beta folding pattern with a central beta-sheet), an NAD(P)(H)-binding region, and a structurally diverse C-terminal region. Classical SDRs are typically about 250 residues long, while extended SDRS are approximately 350 residues. Sequence identity between different SDR enzymes are typically in the 15-30% range, but the enzymes share the Rossmann fold NAD-binding motif and characteristic NAD-binding and catalytic sequence patterns. These enzymes have a 3-glycine N-terminal NAD(P)(H)-binding pattern (typically, TGxxxGxG in classical SDRs and TGxxGxxG in extended SDRs), while substrate binding is in the C-terminal region. A critical catalytic Tyr residue (Tyr-151, human 15-hydroxyprostaglandin dehydrogenase (15-PGDH) numbering), is often found in a conserved YXXXK pattern. In addition to the Tyr and Lys, there is often an upstream Ser (Ser-138, 15-PGDH numbering) and/or an Asn (Asn-107, 15-PGDH numbering) or additional Ser, contributing to the active site. Substrates for these enzymes include sugars, steroids, alcohols, and aromatic compounds. The standard reaction mechanism is a proton relay involving the conserved Tyr and Lys, as well as Asn (or Ser). Some SDR family members, including 17 beta-hydroxysteroid dehydrogenase contain an additional helix-turn-helix motif that is not generally found among SDRs.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568966264  27 LQDKYVFITGCDSGFGNLLARQLDRRGM-RVLAACLTEKGAEELRNKTSDRLETVILDVTKTESIVAATQWVKErvgnrg 105
Cdd:cd05354    1 IKDKTVLVTGANRGIGKAFVESLLAHGAkKVYAAVRDPGSAAHLVAKYGDKVVPLRLDVTDPESIKAAAAQAKD------ 74

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568966264 106 LWGLVNNAGISTPSGPNEWMKKQDFARVLDVNLLGMIEVTLSMLPLVRKA-RGRVVNVSSVMGRMSFFG-GGYCISKYGV 183
Cdd:cd05354   75 VDVVINNAGVLKPATLLEEGALEALKQEMDVNVFGLLRLAQAFAPVLKANgGGAIVNLNSVASLKNFPAmGTYSASKSAA 154

                        170       180
                 ....*....|....*....|....*.
gi 568966264 184 EAFSDSLRSE-KPKRIG-QEVQQGPV 207
Cdd:cd05354  155 YSLTQGLRAElAAQGTLvLSVHPGPI 180

classical (c) SDR, subgroup 5; These proteins are members of the classical SDR family, with a canonical active site tetrad and a typical Gly-rich NAD-binding motif. SDRs are a functionally diverse family of oxidoreductases that have a single domain with a structurally conserved Rossmann fold (alpha/beta folding pattern with a central beta-sheet), an NAD(P)(H)-binding region, and a structurally diverse C-terminal region. Classical SDRs are typically about 250 residues long, while extended SDRs are approximately 350 residues. Sequence identity between different SDR enzymes are typically in the 15-30% range, but the enzymes share the Rossmann fold NAD-binding motif and characteristic NAD-binding and catalytic sequence patterns. These enzymes 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 (15-PGDH) numbering). In addition to the Tyr and Lys, there is often an upstream Ser (Ser-138, 15-PGDH numbering) and/or an Asn (Asn-107, 15-PGDH numbering) 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. Extended SDRs have additional elements in the C-terminal region, 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. Some atypical SDRs have lost catalytic activity and/or have an unusual NAD(P)-binding motif and missing or unusual active site residues. Reactions catalyzed within the SDR family include isomerization, decarboxylation, epimerization, C=N bond reduction, dehydratase activity, dehalogenation, Enoyl-CoA reduction, and carbonyl-alcohol oxidoreduction.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568966264  30 KYVFITGCDSGFGNLLARQLDRRGMRVLaacLT-------EKGAEELRNKTSDRLETVILDVTKTESIVAATQWVKERVG 102
Cdd:cd05346    1 KTVLITGASSGIGEATARRFAKAGAKLI---LTgrraerlQELADELGAKFPVKVLPLQLDVSDRESIEAALENLPEEFR 77

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568966264 103 NrgLWGLVNNAGISTPSGPNEWMKKQDFARVLDVNLLGMIEVTLSMLP-LVRKARGRVVNVSSVMGRMSFFGGG-YCISK 180
Cdd:cd05346   78 D--IDILVNNAGLALGLDPAQEADLEDWETMIDTNVKGLLNVTRLILPiMIARNQGHIINLGSIAGRYPYAGGNvYCATK 155

                        170
                 ....*....|...
gi 568966264 181 YGVEAFSDSLRSE 193
Cdd:cd05346  156 AAVRQFSLNLRKD 168

3-ketodihydrosphingosine reductase (KDSR) and related proteins, classical (c) SDR; These proteins include members identified as KDSR, ribitol type dehydrogenase, and others. The group shows strong conservation of the active site tetrad and glycine rich NAD-binding motif of the classical SDRs. SDRs are a functionally diverse family of oxidoreductases that have a single domain with a structurally conserved Rossmann fold (alpha/beta folding pattern with a central beta-sheet), an NAD(P)(H)-binding region, and a structurally diverse C-terminal region. Classical SDRs are typically about 250 residues long, while extended SDRs are approximately 350 residues. Sequence identity between different SDR enzymes are typically in the 15-30% range, but the enzymes share the Rossmann fold NAD-binding motif and characteristic NAD-binding and catalytic sequence patterns. These enzymes 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 (15-PGDH) numbering). In addition to the Tyr and Lys, there is often an upstream Ser (Ser-138, 15-PGDH numbering) and/or an Asn (Asn-107, 15-PGDH numbering) 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. Extended SDRs have additional elements in the C-terminal region, 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. Some atypical SDRs have lost catalytic activity and/or have an unusual NAD(P)-binding motif and missing or unusual active site residues. Reactions catalyzed within the SDR family include isomerization, decarboxylation, epimerization, C=N bond reduction, dehydratase activity, dehalogenation, Enoyl-CoA reduction, and carbonyl-alcohol oxidoreduction.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568966264  29 DKYVFITGCDSGFGNLLARQLDRRGMRVLAACLTE----KGAEELR---NKTSDRLETVILDVTKTESIVAATQWVKERV 101
Cdd:cd08939    1 GKHVLITGGSSGIGKALAKELVKEGANVIIVARSEskleEAVEEIEaeaNASGQKVSYISADLSDYEEVEQAFAQAVEKG 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568966264 102 GNRGLwgLVNNAGISTPsGPNEWMKKQDFARVLDVNLLGMIEVTLSMLPLVRKAR-GRVVNVSSVMGRMSFFG-GGYCIS 179
Cdd:cd08939   81 GPPDL--VVNCAGISIP-GLFEDLTAEEFERGMDVNYFGSLNVAHAVLPLMKEQRpGHIVFVSSQAALVGIYGySAYCPS 157

                        170       180
                 ....*....|....*....|
gi 568966264 180 KYGVEAFSDSLRSE-KPKRI 198
Cdd:cd08939  158 KFALRGLAESLRQElKPYNI 177

SDR family oxidoreductase;

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568966264  32 VFITGCDSGFGNLLARQLDRRGMRVLAaclTEKGAEELRNKTSDRLETVILDVTKTESIVAATQWVKERVGnrGLWGLVN 111
Cdd:PRK05693   4 VLITGCSSGIGRALADAFKAAGYEVWA---TARKAEDVEALAAAGFTAVQLDVNDGAALARLAEELEAEHG--GLDVLIN 78

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568966264 112 NAGIST--P--SGPNEWMKKQdfarvLDVNLLGMIEVTLSMLPLVRKARGRVVNVSSVMGRMSF-FGGGYCISKYGVEAF 186
Cdd:PRK05693  79 NAGYGAmgPllDGGVEAMRRQ-----FETNVFAVVGVTRALFPLLRRSRGLVVNIGSVSGVLVTpFAGAYCASKAAVHAL 153

                 ....*..
gi 568966264 187 SDSLRSE 193
Cdd:PRK05693 154 SDALRLE 160

short chain dehydrogenase; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568966264  27 LQDKYVFITGCDSGFGNLLARQLDRRGMRVLAACLTEKG----AEELRNKTSDRLeTVILDVTKTESIVAATQWVKERVG 102
Cdd:PRK07109   6 IGRQVVVITGASAGVGRATARAFARRGAKVVLLARGEEGlealAAEIRAAGGEAL-AVVADVADAEAVQAAADRAEEELG 84

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568966264 103 NRGLWglVNNAGISTpSGPNEWMKKQDFARVLDVNLLGMIEVTLSMLP-LVRKARGRVVNVSSVMGRMSF-FGGGYCISK 180
Cdd:PRK07109  85 PIDTW--VNNAMVTV-FGPFEDVTPEEFRRVTEVTYLGVVHGTLAALRhMRPRDRGAIIQVGSALAYRSIpLQSAYCAAK 161

                        170
                 ....*....|...
gi 568966264 181 YGVEAFSDSLRSE 193
Cdd:PRK07109 162 HAIRGFTDSLRCE 174

short chain dehydrogenase; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568966264  28 QDKYVFITGCDSGFGNLLARQLDRRGMRVLAACLTEKGAeelrnKTSDRLETVILDVTKTESIVAATQWVKERVGNRGLw 107
Cdd:PRK06179   3 NSKVALVTGASSGIGRATAEKLARAGYRVFGTSRNPARA-----APIPGVELLELDVTDDASVQAAVDEVIARAGRIDV- 76

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568966264 108 gLVNNAGISTPSGPNEWMKKQDfARVLDVNLLGMIEVTLSMLPLVRKAR-GRVVNVSSVMGRM-SFFGGGYCISKYGVEA 185
Cdd:PRK06179  77 -LVNNAGVGLAGAAEESSIAQA-QALFDTNVFGILRMTRAVLPHMRAQGsGRIINISSVLGFLpAPYMALYAASKHAVEG 154

                 ....*...
gi 568966264 186 FSDSLRSE 193
Cdd:PRK06179 155 YSESLDHE 162

SDR family oxidoreductase;

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568966264  33 FITGCDSGFGNLLARQLDRRGMRVlAACLTEKGA-EELRNKTSDRLETVILDVTKTESIVAATQWVKERVGNRGLwgLVN 111
Cdd:PRK06482   6 FITGASSGFGRGMTERLLARGDRV-AATVRRPDAlDDLKARYGDRLWVLQLDVTDSAAVRAVVDRAFAALGRIDV--VVS 82