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 392841219  25 GGLDYLVLNHIGGAPAGTRARSPQATRWLMQVNFVSYVQLTSRALPSLTD-SKGSLVVVSSLLGRVPTSFSTPYSAAKFA 103
Cdd:cd05332   80 GGLDILINNAGISMRSLFHDTSIDVDRKIMEVNYFGPVALTKAALPHLIErSQGSIVVVSSIAGKIGVPFRTAYAASKHA 159

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*
gi 392841219 104 LDGFFGSLRRELdvQDVNVAITMCVLGLRDRASAAEAVRSSTSRP 148
Cdd:cd05332  160 LQGFFDSLRAEL--SEPNISVTVVCPGLIDTNIAMNALSGDGSMS 202

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 392841219  25 GGLDYLVLNHIGGAPAGTRARSPQATRWLMQVNFVSYVQLTSRALPSLTD-SKGSLVVVSSLLGRVPTSFSTPYSAAKFA 103
Cdd:cd05332   80 GGLDILINNAGISMRSLFHDTSIDVDRKIMEVNYFGPVALTKAALPHLIErSQGSIVVVSSIAGKIGVPFRTAYAASKHA 159

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*
gi 392841219 104 LDGFFGSLRRELdvQDVNVAITMCVLGLRDRASAAEAVRSSTSRP 148
Cdd:cd05332  160 LQGFFDSLRAEL--SEPNISVTVVCPGLIDTNIAMNALSGDGSMS 202

SDR family oxidoreductase;

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392841219  25 GGLDYLVLNhiggapAGTRARSPQAT-------RWLMQVNFVSYVQLTSRALPSLTDSKGSLVVVSSLLGRVPTSFSTPY 97
Cdd:PRK06181  77 GGIDILVNN------AGITMWSRFDEltdlsvfERVMRVNYLGAVYCTHAALPHLKASRGQIVVVSSLAGLTGVPTRSGY 150

                         90       100
                 ....*....|....*....|....*..
gi 392841219  98 SAAKFALDGFFGSLRRELDVQDVNVAI 124
Cdd:PRK06181 151 AASKHALHGFFDSLRIELADDGVAVTV 177

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 392841219  25 GGLDYLVLNHIGGAPAGTRARSPQATRWLMQVNFVSYVQLTSRALPSLTD-SKGSLVVVSSLLGRVPTSFSTPYSAAKFA 103
Cdd:cd05332   80 GGLDILINNAGISMRSLFHDTSIDVDRKIMEVNYFGPVALTKAALPHLIErSQGSIVVVSSIAGKIGVPFRTAYAASKHA 159

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*
gi 392841219 104 LDGFFGSLRRELdvQDVNVAITMCVLGLRDRASAAEAVRSSTSRP 148
Cdd:cd05332  160 LQGFFDSLRAEL--SEPNISVTVVCPGLIDTNIAMNALSGDGSMS 202

SDR family oxidoreductase;

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392841219  25 GGLDYLVLNhiggapAGTRARSPQAT-------RWLMQVNFVSYVQLTSRALPSLTDSKGSLVVVSSLLGRVPTSFSTPY 97
Cdd:PRK06181  77 GGIDILVNN------AGITMWSRFDEltdlsvfERVMRVNYLGAVYCTHAALPHLKASRGQIVVVSSLAGLTGVPTRSGY 150

                         90       100
                 ....*....|....*....|....*..
gi 392841219  98 SAAKFALDGFFGSLRRELDVQDVNVAI 124
Cdd:PRK06181 151 AASKHALHGFFDSLRIELADDGVAVTV 177

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 392841219  25 GGLDYLVLNHIGGAPAGTRARSPQATRWLMQVNFVSYVQLTSRALPSL-TDSKGSLVVVSSLLGRVPTSFSTPYSAAKFA 103
Cdd:cd05233   73 GRLDILVNNAGIARPGPLEELTDEDWDRVLDVNLTGVFLLTRAALPHMkKQGGGRIVNISSVAGLRPLPGQAAYAASKAA 152

                         90
                 ....*....|..
gi 392841219 104 LDGFFGSLRREL 115
Cdd:cd05233  153 LEGLTRSLALEL 164

NADP-dependent 3-hydroxy acid dehydrogenase YdfG [Energy production and conversion]; NADP-dependent 3-hydroxy acid dehydrogenase YdfG is part of the Pathway/BioSystem: Pyrimidine degradation

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392841219  25 GGLDYLVLNHIGGAPAGTRARSPQATRWLMQVNFVSYVQLTSRALPSLTDSK-GSLVVVSSLLGRVPTSFSTPYSAAKFA 103
Cdd:COG4221   78 GRLDVLVNNAGVALLGPLEELDPEDWDRMIDVNVKGVLYVTRAALPAMRARGsGHIVNISSIAGLRPYPGGAVYAATKAA 157

                         90       100
                 ....*....|....*....|.
gi 392841219 104 LDGFFGSLRRELDVQDVNVAI 124
Cdd:COG4221  158 VRGLSESLRAELRPTGIRVTV 178

NAD(P)-dependent dehydrogenase, short-chain alcohol dehydrogenase family [Lipid transport and metabolism]; NAD(P)-dependent dehydrogenase, short-chain alcohol dehydrogenase family is part of the Pathway/BioSystem: Fatty acid biosynthesis

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392841219  25 GGLDYLVLNHIGGAPAGTRARSPQATRWLMQVNFVSYVQLTSRALPSLTDSK-GSLVVVSSLLGRVPTSFSTPYSAAKFA 103
Cdd:COG1028   82 GRLDILVNNAGITPPGPLEELTEEDWDRVLDVNLKGPFLLTRAALPHMRERGgGRIVNISSIAGLRGSPGQAAYAASKAA 161

                         90
                 ....*....|..
gi 392841219 104 LDGFFGSLRREL 115
Cdd:COG1028  162 VVGLTRSLALEL 173

SDR family oxidoreductase;

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392841219  24 PGGLDYLVLNHIGGAPAGTRARSPQATRWLMQVNFVSYVQLTSRALPSL-TDSKGSLVVVSSLLGRVPTSFSTPYSAAKF 102
Cdd:PRK05993  74 GGRLDALFNNGAYGQPGAVEDLPTEALRAQFEANFFGWHDLTRRVIPVMrKQGQGRIVQCSSILGLVPMKYRGAYNASKF 153

                         90       100
                 ....*....|....*....|..
gi 392841219 103 ALDGFFGSLRRELDVQDVNVAI 124
Cdd:PRK05993 154 AIEGLSLTLRMELQGSGIHVSL 175

short chain dehydrogenase; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392841219  25 GGLDYLVlNHIGGAP--AGTRARSPQATRWLMQVNFVSYVQLTSRALPSLTDSK--GSLVVVSSLLGRVPTSFSTPYSAA 100
Cdd:PRK12829  85 GGLDVLV-NNAGIAGptGGIDEITPEQWEQTLAVNLNGQFYFARAAVPLLKASGhgGVIIALSSVAGRLGYPGRTPYAAS 163

                         90       100
                 ....*....|....*....|..
gi 392841219 101 KFALDGFFGSLRRELDVQDVNV 122
Cdd:PRK12829 164 KWAVVGLVKSLAIELGPLGIRV 185

clavulanic acid dehydrogenase (CAD), classical (c) SDR; CAD catalyzes the NADP-dependent reduction of clavulanate-9-aldehyde to clavulanic acid, a beta-lactamase inhibitor. 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 392841219  25 GGLDYLVLNhiggapAGTRARSP----QATRW--LMQVNFVSYVQLTSRALP-SLTDSKGSLVVVSSLLGRVPTSFSTPY 97
Cdd:cd08934   79 GRLDILVNN------AGIMLLGPvedaDTTDWtrMIDTNLLGLMYTTHAALPhHLLRNKGTIVNISSVAGRVAVRNSAVY 152

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 392841219  98 SAAKFALDGFFGSLRRELDVQDVNVAIT---MCVLGLRDRAS-----AAEAVRSSTSRPRQPE 152
Cdd:cd08934  153 NATKFGVNAFSEGLRQEVTERGVRVVVIepgTVDTELRDHIThtitkEAYEERISTIRKLQAE 215

classical (c) SDR, subgroup 11; 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 392841219  25 GGLDYLVLNhiGGAPAGTRARSPQATRW--LMQVNFVSYVQLTSRALPSLTDSKGSLVVVSSLLGRVPTSFSTPYSAAKF 102
Cdd:cd05364   82 GRLDILVNN--AGILAKGGGEDQDIEEYdkVMNLNLRAVIYLTKLAVPHLIKTKGEIVNVSSVAGGRSFPGVLYYCISKA 159

                         90       100
                 ....*....|....*....|
gi 392841219 103 ALDGFFGSLRRELDVQDVNV 122
Cdd:cd05364  160 ALDQFTRCTALELAPKGVRV 179

insect type alcohol dehydrogenase (ADH)-like, classical (c) SDRs; This subgroup contains insect type ADH, and 15-hydroxyprostaglandin dehydrogenase (15-PGDH) type I; these proteins are classical SDRs. ADH catalyzes the NAD+-dependent oxidation of alcohols to aldehydes/ketones. This subgroup is distinct from the zinc-dependent alcohol dehydrogenases of the medium chain dehydrogenase/reductase family, and evolved in fruit flies to allow the digestion of fermenting fruit. 15-PGDH catalyzes the NAD-dependent interconversion of (5Z,13E)-(15S)-11alpha,15-dihydroxy-9-oxoprost-13-enoate and (5Z,13E)-11alpha-hydroxy-9,15-dioxoprost-13-enoate, and has a typical SDR glycine-rich NAD-binding motif, which is not fully present in ADH. 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 392841219   9 LGALFFAYYwddnFDPGGLDYLVLN--HIGGAPAGTRARSPQATRWLMQVNFVSYVQLTSRALPSLTDSK----GSLVVV 82
Cdd:cd05323   64 LAAAFKKAI----EKFGRVDILINNagILDEKSYLFAGKLPPPWEKTIDVNLTGVINTTYLALHYMDKNKggkgGVIVNI 139

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*.
gi 392841219  83 SSLLGRVPTSFSTPYSAAKFALDGFFGSLRRELDVQDvNVAI-TMC 127
Cdd:cd05323  140 GSVAGLYPAPQFPVYSASKHGVVGFTRSLADLLEYKT-GVRVnAIC 184

SDR family oxidoreductase;

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392841219  25 GGLDYLVLNhIGGAPAGTRARS-PQATRWLMQVNFVSYVQLTSRALPSLTDSKGSLVVVSSLLGRVPTSFSTPYSAAKFA 103
Cdd:PRK08219  70 GRLDVLVHN-AGVADLGPVAEStVDEWRATLEVNVVAPAELTRLLLPALRAAHGHVVFINSGAGLRANPGWGSYAASKFA 148

                         90
                 ....*....|.
gi 392841219 104 LDGFFGSLRRE 114
Cdd:PRK08219 149 LRALADALREE 159

Porcine testicular carbonyl reductase (PTCR)-like, classical (c) SDRs; PTCR is a classical SDR which catalyzes the NADPH-dependent reduction of ketones on steroids and prostaglandins. Unlike most SDRs, PTCR functions as a monomer. This subgroup also includes human carbonyl reductase 1 (CBR1) and CBR3. CBR1 is an NADPH-dependent SDR with broad substrate specificity and may be responsible for the in vivo reduction of quinones, prostaglandins, and other carbonyl-containing compounds. In addition it includes poppy NADPH-dependent salutaridine reductase which catalyzes the stereospecific reduction of salutaridine to 7(S)-salutaridinol in the biosynthesis of morphine, and Arabidopsis SDR1,a menthone reductase, which catalyzes the reduction of menthone to neomenthol, a compound with antimicrobial activity; SDR1 can also carry out neomenthol oxidation. 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, 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 392841219  23 DPGGLDYLVlNHIGGAPAGTRARSP--QATRWLMQVNFVSYVQLTSRALPSLTDSKGSLVV-VSSLLGrvptSFSTPYSA 99
Cdd:cd05324   75 KYGGLDILV-NNAGIAFKGFDDSTPtrEQARETMKTNFFGTVDVTQALLPLLKKSPAGRIVnVSSGLG----SLTSAYGV 149

                         90       100
                 ....*....|....*....|...
gi 392841219 100 AKFALDGFFGSLRRELDVQDVNV 122
Cdd:cd05324  150 SKAALNALTRILAKELKETGIKV 172

short chain dehydrogenase; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392841219  25 GGLDYLVLNhIGGAPAGTRARS-PQATRWLMQVNFVSyVQLTSRA-LPSLTDSKGSLVVVSSLLGRVPTSFSTPYSAAKF 102
Cdd:PRK05872  84 GGIDVVVAN-AGIASGGSVAQVdPDAFRRVIDVNLLG-VFHTVRAtLPALIERRGYVLQVSSLAAFAAAPGMAAYCASKA 161

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|...
gi 392841219 103 ALDGFFGSLRRELDVQDVNVAI-------TMCVLGLRDRASAAEAVRSSTSRP 148
Cdd:PRK05872 162 GVEAFANALRLEVAHHGVTVGSaylswidTDLVRDADADLPAFRELRARLPWP 214

short chain dehydrogenase; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392841219  25 GGLDYLVLNHIGGAPAGTRARSPQATRWLMQVNFVSYVQLTSRALPSL-TDSKGSLVVVSSLLGRVPTSFSTPYSAAKFA 103
Cdd:PRK06179  72 GRIDVLVNNAGVGLAGAAEESSIAQAQALFDTNVFGILRMTRAVLPHMrAQGSGRIINISSVLGFLPAPYMALYAASKHA 151

                         90       100
                 ....*....|....*....|.
gi 392841219 104 LDGFFGSLRRELDVQDVNVAI 124
Cdd:PRK06179 152 VEGYSESLDHEVRQFGIRVSL 172

retinal dehydrogenase-like, classical (c) SDR; These classical SDRs includes members identified as retinol dehydrogenases, which convert retinol to retinal, a property that overlaps with 17betaHSD activity. 17beta-dehydrogenases are a group of isozymes that catalyze activation and inactivation of estrogen and androgens, and include members of the short-chain dehydrogenases/reductase family. 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 392841219  25 GGLDYLVlNHIGGAP--AGTRARSPQATRWLMQVNFVSYVQLTSRALPSLTDSKGSLVVVSSLLGRVPTSFSTPYSAAKF 102
Cdd:cd08933   86 GRIDCLV-NNAGWHPphQTTDETSAQEFRDLLNLNLISYFLASKYALPHLRKSQGNIINLSSLVGSIGQKQAAPYVATKG 164

                 ..
gi 392841219 103 AL 104
Cdd:cd08933  165 AI 166

SDR family oxidoreductase;

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392841219  25 GGLDYLVLNHIGGAPAGTRARSPQATRWLMQVNFVSYVQLTSRALPSLTDSKGSLVVVSSLLGRVPTSFSTPYSAAKFAL 104
Cdd:PRK07326  81 GGLDVLIANAGVGHFAPVEELTPEEWRLVIDTNLTGAFYTIKAAVPALKRGGGYIINISSLAGTNFFAGGAAYNASKFGL 160

                         90       100
                 ....*....|....*....|..
gi 392841219 105 DGFFGSLRRELDVQDVNVAITM 126
Cdd:PRK07326 161 VGFSEAAMLDLRQYGIKVSTIM 182

short chain dehydrogenase; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392841219  25 GGLDYLVlNHIGG--APAGTRARSPQAtRWL--MQVNFVSYVQLTSRALPSLTDS-KGSLVVVSSLLGRVPTSFST-PYS 98
Cdd:PRK06523  76 GGVDILV-HVLGGssAPAGGFAALTDE-EWQdeLNLNLLAAVRLDRALLPGMIARgSGVIIHVTSIQRRLPLPESTtAYA 153

                         90       100
                 ....*....|....*....|....
gi 392841219  99 AAKFALDGFFGSLRRELDVQDVNV 122
Cdd:PRK06523 154 AAKAALSTYSKSLSKEVAPKGVRV 177

sepiapterin reductase (SPR)-like, classical (c) SDRs; Human SPR, a member of the SDR family, catalyzes the NADP-dependent reduction of sepiaptern to 7,8-dihydrobiopterin (BH2). In addition to SPRs, this subgroup also contains Bacillus cereus yueD, a benzil reductase, which catalyzes the stereospecific reduction of benzil to (S)-benzoin. 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 392841219  27 LDYLVLNHIGGAPAGTRAR-SPQATRWLMQVNFVSYVQLTSRALPSLTDS--KGSLVVVSSLLGRVPTSFSTPYSAAKFA 103
Cdd:cd05367   78 RDLLINNAGSLGPVSKIEFiDLDELQKYFDLNLTSPVCLTSTLLRAFKKRglKKTVVNVSSGAAVNPFKGWGLYCSSKAA 157

                         90       100
                 ....*....|....*....|.
gi 392841219 104 LDGFFGSLRREL-DVQDVNVA 123
Cdd:cd05367  158 RDMFFRVLAAEEpDVRVLSYA 178

short chain dehydrogenase; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392841219  23 DPGGLDYLVlNHIGGAPAGTRA-RSPQATRWLMQVNFVSYVQLTSRALPSLTD-SKGSLVVVSSLLGRVPTSFSTPYSAA 100
Cdd:PRK07825  75 DLGPIDVLV-NNAGVMPVGPFLdEPDAVTRRILDVNVYGVILGSKLAAPRMVPrGRGHVVNVASLAGKIPVPGMATYCAS 153

                         90       100
                 ....*....|....*....|....*.
gi 392841219 101 KFALDGFFGSLRRELDVQDVNVAITM 126
Cdd:PRK07825 154 KHAVVGFTDAARLELRGTGVHVSVVL 179

17-beta-hydroxysteroid dehydrogenases (17beta-HSDs) types -1, -3, and -12, -like, classical (c) SDRs; This subgroup includes various 17-beta-hydroxysteroid dehydrogenases and 3-ketoacyl-CoA reductase, these are members of the SDR family, and contain the canonical active site tetrad and glycine-rich NAD-binding motif of the classical SDRs. 3-ketoacyl-CoA reductase (KAR, aka 17beta-HSD type 12, encoded by HSD17B12) acts in fatty acid elongation; 17beta- hydroxysteroid dehydrogenases are isozymes that catalyze activation and inactivation of estrogen and androgens, and include members of the SDR family. 17beta-estradiol dehydrogenase (aka 17beta-HSD type 1, encoded by HSD17B1) converts estrone to estradiol. Estradiol is the predominant female sex hormone. 17beta-HSD type 3 (aka testosterone 17-beta-dehydrogenase 3, encoded by HSD17B3) catalyses the reduction of androstenedione to testosterone, it also accepts estrogens as substrates. This subgroup also contains a putative steroid dehydrogenase let-767 from Caenorhabditis elegans, mutation in which results in hypersensitivity to cholesterol limitation. 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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 392841219  53 LMQVNFVSYVQLTSRALPSLTD-SKGSLVVVSSLLGRVPTSFSTPYSAAKFALDGFFGSLRRELDVQDVNV 122
Cdd:cd05356  107 IINVNVMATLKMTRLILPGMVKrKKGAIVNISSFAGLIPTPLLATYSASKAFLDFFSRALYEEYKSQGIDV 177

short chain dehydrogenase; Validated

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392841219  56 VNFVSYVQLTSRALPSLTDSK-GSLVVVSSLLGRVPTSFSTPYSAAKFALDGFFGSLRRELDVQDVNVAI 124
Cdd:PRK06182 104 VNLFGAARLTQLVLPHMRAQRsGRIINISSMGGKIYTPLGAWYHATKFALEGFSDALRLEVAPFGIDVVV 173

tropinone reductase-I and II (TR-1, and TR-II)-like, classical (c) SDRs; This subgroup includes TR-I and TR-II; these proteins are members of the SDR family. TRs catalyze the NADPH-dependent reductions of the 3-carbonyl group of tropinone, to a beta-hydroxyl group. TR-I and TR-II produce different stereoisomers from tropinone, TR-I produces tropine (3alpha-hydroxytropane), and TR-II, produces pseudotropine (sigma-tropine, 3beta-hydroxytropane). 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 392841219  20 DNFDpGGLDYLVLNHIGGAPAGTRARSPQATRWLMQVNFVSYVQLTSRALPSLTDS-KGSLVVVSSLLGRVPTSFSTPYS 98
Cdd:cd05329   79 SHFG-GKLNILVNNAGTNIRKEAKDYTEEDYSLIMSTNFEAAYHLSRLAHPLLKASgNGNIVFISSVAGVIAVPSGAPYG 157

                 ....*..
gi 392841219  99 AAKFALD 105
Cdd:cd05329  158 ATKGALN 164

Short-chain dehydrogenases/reductases (SDR); 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 (KR) domains of fatty acid synthase have a GGXGXXG NAD(P)-binding motif and an altered active site motif (YXXXN). Fungal type KRs 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 392841219  27 LDYLVlnHIGGAPAGTRARSPQATRW--LMQVNFVSYVQLTSRALPSLTD-SKGSLVVVSSLLGRVPTSFSTPYSAAKFA 103
Cdd:cd02266   32 RDVVV--HNAAILDDGRLIDLTGSRIerAIRANVVGTRRLLEAARELMKAkRLGRFILISSVAGLFGAPGLGGYAASKAA 109

                         90       100
                 ....*....|....*....|....
gi 392841219 104 LDGFFGSLRRELDVQDVNVAITMC 127
Cdd:cd02266  110 LDGLAQQWASEGWGNGLPATAVAC 133

SDR family oxidoreductase;

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392841219  26 GLDYLVL-NHIGGAPAGTRARSPQA-TRWLMQVNFVSYVQLTSRALPSLT-DSKGSLVVVSSLLGRVPTSFSTPYSAAKF 102
Cdd:PRK09291  71 EWDVDVLlNNAGIGEAGAVVDIPVElVRELFETNVFGPLELTQGFVRKMVaRGKGKVVFTSSMAGLITGPFTGAYCASKH 150

                         90       100
                 ....*....|....*....|.
gi 392841219 103 ALDGFFGSLRRELDVQDVNVA 123
Cdd:PRK09291 151 ALEAIAEAMHAELKPFGIQVA 171

Porcine peroxisomal carbonyl reductase like, classical (c) SDR; This subgroup contains porcine peroxisomal carbonyl reductase and similar proteins. The porcine enzyme efficiently reduces retinals. This subgroup also includes human dehydrogenase/reductase (SDR family) member 4 (DHRS4), and human DHRS4L1. DHRS4 is a peroxisomal enzyme with 3beta-hydroxysteroid dehydrogenase activity; it catalyzes the reduction of 3-keto-C19/C21-steroids into 3beta-hydroxysteroids more efficiently than it does the retinal reduction. The human DHRS4 gene cluster contains DHRS4, DHRS4L2 and DHRS4L1. DHRS4L2 and DHRS4L1 are paralogs of DHRS4, DHRS4L2 being the most recent member. 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 392841219  25 GGLDYLVLNHIGGAPAGTRARSPQATrW--LMQVNFVSYVQLTSRALPSLTD-SKGSLVVVSSLLGRVPTSFSTPYSAAK 101
Cdd:cd08936   86 GGVDILVSNAAVNPFFGNILDSTEEV-WdkILDVNVKATALMTKAVVPEMEKrGGGSVVIVSSVAAFHPFPGLGPYNVSK 164

                         90       100
                 ....*....|....*....|.
gi 392841219 102 FALDGFFGSLRRELDVQDVNV 122
Cdd:cd08936  165 TALLGLTKNLAPELAPRNIRV 185

SDR family oxidoreductase;

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 392841219  52 WLMQVNFVSYVQLTSRALPSLTDSKGSLVV-VSSLLGRVPTSFSTPYSAAKFALDGFFGSLRRE 114
Cdd:PRK07454 109 WVIQLNLTSVFQCCSAVLPGMRARGGGLIInVSSIAARNAFPQWGAYCVSKAALAAFTKCLAEE 172

short chain dehydrogenase; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392841219  25 GGLDYLVLNHIGGAPAGTRAR-SPQATRWLMQVNFVSYVQLTSRALPSLTDSKGSLVVVSSLLGRVPTSFSTPYSAAKFA 103
Cdd:PRK07890  81 GRVDALVNNAFRVPSMKPLADaDFAHWRAVIELNVLGTLRLTQAFTPALAESGGSIVMINSMVLRHSQPKYGAYKMAKGA 160