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        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4557649   48 GQWAVITGAGDGIGKAYSFELAKRGLNVVLISRTLEKLEAIATEIERTTGRSVKIIQADFT-KDDIYEHIKEKLAGLEIG 126
Cdd:cd05356   1 GTWAVVTGATDGIGKAYAEELAKRGFNVILISRTQEKLDAVAKEIEEKYGVETKTIAADFSaGDDIYERIEKELEGLDIG 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4557649  127 ILVNNVGMLPNLlPSHFLNAP-DEIQSLIHCNITSVVKMTQLILKHMESRQKGLILNISSGIALFPWPLYSMYSASKAFV 205
Cdd:cd05356  81 ILVNNVGISHSI-PEYFLETPeDELQDIINVNVMATLKMTRLILPGMVKRKKGAIVNISSFAGLIPTPLLATYSASKAFL 159

                       170       180       190       200       210       220       230
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 4557649  206 CAFSKALQEEYKAKEVIIQVLTPYAVSTAMTKYLNTNVITKTADEFVKESLNYVTIGGETCGCLAHEILAGFLSLIPAW 284
Cdd:cd05356 160 DFFSRALYEEYKSQGIDVQSLLPYLVATKMSKIRKSSLFVPSPEQFVRSALNTLGLSKRTTGYWSHALQGWVARLVPEW 238

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        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4557649   48 GQWAVITGAGDGIGKAYSFELAKRGLNVVLISRTLEKLEAIATEIERTTGRSVKIIQADFT-KDDIYEHIKEKLAGLEIG 126
Cdd:cd05356   1 GTWAVVTGATDGIGKAYAEELAKRGFNVILISRTQEKLDAVAKEIEEKYGVETKTIAADFSaGDDIYERIEKELEGLDIG 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4557649  127 ILVNNVGMLPNLlPSHFLNAP-DEIQSLIHCNITSVVKMTQLILKHMESRQKGLILNISSGIALFPWPLYSMYSASKAFV 205
Cdd:cd05356  81 ILVNNVGISHSI-PEYFLETPeDELQDIINVNVMATLKMTRLILPGMVKRKKGAIVNISSFAGLIPTPLLATYSASKAFL 159

                       170       180       190       200       210       220       230
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 4557649  206 CAFSKALQEEYKAKEVIIQVLTPYAVSTAMTKYLNTNVITKTADEFVKESLNYVTIGGETCGCLAHEILAGFLSLIPAW 284
Cdd:cd05356 160 DFFSRALYEEYKSQGIDVQSLLPYLVATKMSKIRKSSLFVPSPEQFVRSALNTLGLSKRTTGYWSHALQGWVARLVPEW 238

Short-chain dehydrogenase [General function prediction only];

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4557649   47 MGQWAVITGAGDGIGKAYSFELAKRGLNVVLISRTLEKLEAIATEIeRTTGRSVKIIQADFTKDD----IYEHIKEKLAG 122
Cdd:COG0300   4 TGKTVLITGASSGIGRALARALAARGARVVLVARDAERLEALAAEL-RAAGARVEVVALDVTDPDavaaLAEAVLARFGP 82

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4557649  123 leIGILVNNVGMLPnllPSHFLNAP-DEIQSLIHCNITSVVKMTQLILKHMESRQKGLILNISSGIALFPWPLYSMYSAS 201
Cdd:COG0300  83 --IDVLVNNAGVGG---GGPFEELDlEDLRRVFEVNVFGPVRLTRALLPLMRARGRGRIVNVSSVAGLRGLPGMAAYAAS 157

                       170       180       190
                ....*....|....*....|....*....|....*.
gi 4557649  202 KAFVCAFSKALQEEYKAKEVIIQVLTPYAVSTAMTK 237
Cdd:COG0300 158 KAALEGFSESLRAELAPTGVRVTAVCPGPVDTPFTA 193

sepiapterin reductase; This model describes sepiapterin reductase, a member of the short chain dehydrogenase/reductase family. The enzyme catalyzes the last step in the biosynthesis of tetrahydrobiopterin. A similar enzyme in Bacillus cereus was isolated for its ability to convert benzil to (S)-benzoin, a property sepiapterin reductase also shares. Cutoff scores for this model are set such that benzil reductase scores between trusted and noise cutoffs.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4557649     51 AVITGAGDGIGKAYSFELAKRGLN----VVLISRTLEKLEAIATEIERTT-GRSVKIIQADF-TKDDIYEHIKEKLA--- 121
Cdd:TIGR01500   3 CLVTGASRGFGRTIAQELAKCLKSpgsvLVLSARNDEALRQLKAEIGAERsGLRVVRVSLDLgAEAGLEQLLKALRElpr 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4557649    122 --GLEIGILVNNVGMLPNLLP-SHFLNAPDEIQSLIHCNITSVVKMTQLILKHMESRQ--KGLILNISSGIALFPWPLYS 196
Cdd:TIGR01500  83 pkGLQRLLLINNAGTLGDVSKgFVDLSDSTQVQNYWALNLTSMLCLTSSVLKAFKDSPglNRTVVNISSLCAIQPFKGWA 162

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|
gi 4557649    197 MYSASKAFVCAFSKALQEEYKAKEVIIQVLTPYAVSTAMT 236
Cdd:TIGR01500 163 LYCAGKAARDMLFQVLALEEKNPNVRVLNYAPGVLDTDMQ 202

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        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4557649   48 GQWAVITGAGDGIGKAYSFELAKRGLNVVLISRTLEKLEAIATEIERTTGRSVKIIQADFT-KDDIYEHIKEKLAGLEIG 126
Cdd:cd05356   1 GTWAVVTGATDGIGKAYAEELAKRGFNVILISRTQEKLDAVAKEIEEKYGVETKTIAADFSaGDDIYERIEKELEGLDIG 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4557649  127 ILVNNVGMLPNLlPSHFLNAP-DEIQSLIHCNITSVVKMTQLILKHMESRQKGLILNISSGIALFPWPLYSMYSASKAFV 205
Cdd:cd05356  81 ILVNNVGISHSI-PEYFLETPeDELQDIINVNVMATLKMTRLILPGMVKRKKGAIVNISSFAGLIPTPLLATYSASKAFL 159

                       170       180       190       200       210       220       230
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 4557649  206 CAFSKALQEEYKAKEVIIQVLTPYAVSTAMTKYLNTNVITKTADEFVKESLNYVTIGGETCGCLAHEILAGFLSLIPAW 284
Cdd:cd05356 160 DFFSRALYEEYKSQGIDVQSLLPYLVATKMSKIRKSSLFVPSPEQFVRSALNTLGLSKRTTGYWSHALQGWVARLVPEW 238

Short-chain dehydrogenase [General function prediction only];

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4557649   47 MGQWAVITGAGDGIGKAYSFELAKRGLNVVLISRTLEKLEAIATEIeRTTGRSVKIIQADFTKDD----IYEHIKEKLAG 122
Cdd:COG0300   4 TGKTVLITGASSGIGRALARALAARGARVVLVARDAERLEALAAEL-RAAGARVEVVALDVTDPDavaaLAEAVLARFGP 82

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4557649  123 leIGILVNNVGMLPnllPSHFLNAP-DEIQSLIHCNITSVVKMTQLILKHMESRQKGLILNISSGIALFPWPLYSMYSAS 201
Cdd:COG0300  83 --IDVLVNNAGVGG---GGPFEELDlEDLRRVFEVNVFGPVRLTRALLPLMRARGRGRIVNVSSVAGLRGLPGMAAYAAS 157

                       170       180       190
                ....*....|....*....|....*....|....*.
gi 4557649  202 KAFVCAFSKALQEEYKAKEVIIQVLTPYAVSTAMTK 237
Cdd:COG0300 158 KAALEGFSESLRAELAPTGVRVTAVCPGPVDTPFTA 193

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 4557649   51 AVITGAGDGIGKAYSFELAKRGLNVVLISRTLEKLEAIATEIERttGRSVKIIQADFTKDDIYEHIKEKL--AGLEIGIL 128
Cdd:cd05233   1 ALVTGASSGIGRAIARRLAREGAKVVLADRNEEALAELAAIEAL--GGNAVAVQADVSDEEDVEALVEEAleEFGRLDIL 78

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4557649  129 VNNVGMLPnllPSHFLNAPDE-IQSLIHCNITSVVKMTQLILKHMESRQKGLILNISSGIALFPWPLYSMYSASKAFVCA 207
Cdd:cd05233  79 VNNAGIAR---PGPLEELTDEdWDRVLDVNLTGVFLLTRAALPHMKKQGGGRIVNISSVAGLRPLPGQAAYAASKAALEG 155

                       170       180       190
                ....*....|....*....|....*....|
gi 4557649  208 FSKALQEEYKAKEVIIQVLTPYAVSTAMTK 237
Cdd:cd05233 156 LTRSLALELAPYGIRVNAVAPGLVDTPMLA 185

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 4557649   47 MGQWAVITGAGDGIGKAYSFELAKRGLNVVLISRTLEKLEAIATEIERTtGRSVKIIQADFTKDD----IYEHIKEKLAG 122
Cdd:COG1028   5 KGKVALVTGGSSGIGRAIARALAAEGARVVITDRDAEALEAAAAELRAA-GGRALAVAADVTDEAaveaLVAAAVAAFGR 83

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4557649  123 LEIgiLVNNVGMLPnllPSHFLNAPDE-IQSLIHCNITSVVKMTQLILKHMESRQKGLILNISSGIALFPWPLYSMYSAS 201
Cdd:COG1028  84 LDI--LVNNAGITP---PGPLEELTEEdWDRVLDVNLKGPFLLTRAALPHMRERGGGRIVNISSIAGLRGSPGQAAYAAS 158

                       170       180       190
                ....*....|....*....|....*....|....*.
gi 4557649  202 KAFVCAFSKALQEEYKAKEVIIQVLTPYAVSTAMTK 237
Cdd:COG1028 159 KAAVVGLTRSLALELAPRGIRVNAVAPGPIDTPMTR 194

SDR family oxidoreductase;

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4557649    42 SFLRSMgQWAVITGAGDGIGKAYSFELAKRGLNVVLISRTLEKLEAIATEIeRTTGRSVKIIQADFTK-DDIYEHIKEKL 120
Cdd:PRK07454   1 MSLNSM-PRALITGASSGIGKATALAFAKAGWDLALVARSQDALEALAAEL-RSTGVKAAAYSIDLSNpEAIAPGIAELL 78

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4557649   121 A-GLEIGILVNNVGM-LPNLLPSHFLnapDEIQSLIHCNITSVVKMTQLILKHMESRQKGLILNISSGIALFPWPLYSMY 198
Cdd:PRK07454  79 EqFGCPDVLINNAGMaYTGPLLEMPL---SDWQWVIQLNLTSVFQCCSAVLPGMRARGGGLIINVSSIAARNAFPQWGAY 155

                        170       180       190
                 ....*....|....*....|....*....|....*..
gi 4557649   199 SASKAFVCAFSKALQEEYKAKEVIIQVLTPYAVSTAM 235
Cdd:PRK07454 156 CVSKAALAAFTKCLAEEERSHGIRVCTITLGAVNTPL 192

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 4557649   51 AVITGAGDGIGKAYSFELAKRGLNVVLISRTLEKLEAIATEIERTTGRSVKIIQADFTKddiYEHIKEKLAGL-----EI 125
Cdd:cd05346   3 VLITGASSGIGEATARRFAKAGAKLILTGRRAERLQELADELGAKFPVKVLPLQLDVSD---RESIEAALENLpeefrDI 79

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4557649  126 GILVNNVGMLPNLLPSHFLnAPDEIQSLIHCNITSVVKMTQLILKHMESRQKGLILNISSGIALFPWPLYSMYSASKAFV 205
Cdd:cd05346  80 DILVNNAGLALGLDPAQEA-DLEDWETMIDTNVKGLLNVTRLILPIMIARNQGHIINLGSIAGRYPYAGGNVYCATKAAV 158

                       170       180
                ....*....|....*....|....*...
gi 4557649  206 CAFSKALQEEYKAKEVIIQVLTPYAVST 233
Cdd:cd05346 159 RQFSLNLRKDLIGTGIRVTNIEPGLVET 186

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 4557649   48 GQWAVITGAGDGIGKAYSFELAKRGLNVVLISRTLEKLEAIATEIERTTGRsVKIIQADFTK----DDIYEHIKEKLAGL 123
Cdd:cd08934   3 GKVALVTGASSGIGEATARALAAEGAAVAIAARRVDRLEALADELEAEGGK-ALVLELDVTDeqqvDAAVERTVEALGRL 81

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4557649  124 EigILVNNVGMLpnLLPSHFLNAPDEIQSLIHCNITSVVKMTQLILKHMESRQKGLILNISSGIALFPWPLYSMYSASKA 203
Cdd:cd08934  82 D--ILVNNAGIM--LLGPVEDADTTDWTRMIDTNLLGLMYTTHAALPHHLLRNKGTIVNISSVAGRVAVRNSAVYNATKF 157

                       170       180       190       200
                ....*....|....*....|....*....|....*....|....*..
gi 4557649  204 FVCAFSKALQEEYKAKEVIIQVLTPYAVSTAMTKYLnTNVITKTADE 250
Cdd:cd08934 158 GVNAFSEGLRQEVTERGVRVVVIEPGTVDTELRDHI-THTITKEAYE 203

Short-chain dehydrogenase involved in D-alanine esterification of teichoic acids [Cell wall/membrane/envelope biogenesis, Lipid transport and metabolism];

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4557649   53 ITGAGDGIGKAYSFELAKRGLNVVLISRTLEKLEAIATEIERttgrsVKIIQADFTK-DDI---YEHIKEKLAGLeiGIL 128
Cdd:COG3967  10 ITGGTSGIGLALAKRLHARGNTVIITGRREEKLEEAAAANPG-----LHTIVLDVADpASIaalAEQVTAEFPDL--NVL 82

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4557649  129 VNNVGMLPNLLPSHFLNAPDEIQSLIHCNITSVVKMTQLILKHMESRQKGLILNISSGIALFPWPLYSMYSASKAFVCAF 208
Cdd:COG3967  83 INNAGIMRAEDLLDEAEDLADAEREITTNLLGPIRLTAAFLPHLKAQPEAAIVNVSSGLAFVPLAVTPTYSATKAALHSY 162

                       170       180       190       200
                ....*....|....*....|....*....|....*....|....*....
gi 4557649  209 SKALQEEYKAKEV-IIQVLTPyAVSTAMTKYLNTNVITKTADEFVKESL 256
Cdd:COG3967 163 TQSLRHQLKDTSVkVIELAPP-AVDTDLTGGQGGDPRAMPLDEFADEVM 210

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 4557649   52 VITGAGDGIGKAYSFELAKRGLN--VVLISRTLEKLEAiaTEIERTTGRSVKIIQADFTKDD----IYEHIKEKlaGLEI 125
Cdd:cd05367   3 ILTGASRGIGRALAEELLKRGSPsvVVLLARSEEPLQE--LKEELRPGLRVTTVKADLSDAAgveqLLEAIRKL--DGER 78

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4557649  126 GILVNNVGMLPNLLPSHFLNaPDEIQSLIHCNITSVVKMTQLILKHM-ESRQKGLILNISSGIALFPWPLYSMYSASKAF 204
Cdd:cd05367  79 DLLINNAGSLGPVSKIEFID-LDELQKYFDLNLTSPVCLTSTLLRAFkKRGLKKTVVNVSSGAAVNPFKGWGLYCSSKAA 157

                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|
gi 4557649  205 VCAFSKALQEEYkaKEVIIQVLTPYAVSTAMTKYL-NTNVITKTADEFVK 253
Cdd:cd05367 158 RDMFFRVLAAEE--PDVRVLSYAPGVVDTDMQREIrETSADPETRSRFRS 205

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 4557649   52 VITGAGDGIGKAYSFELAKRGLNVVLISRTLEKLEAIATEIERTTGRSVKIIQADFTK-DDIYEHIKEKLAGL-EIGILV 129
Cdd:cd05332   7 IITGASSGIGEELAYHLARLGARLVLSARREERLEEVKSECLELGAPSPHVVPLDMSDlEDAEQVVEEALKLFgGLDILI 86

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4557649  130 NNVGMLpnlLPSHFLNAPDEI-QSLIHCNITSVVKMTQLILKHMESRQKGLILNISSGIALFPWPLYSMYSASKAFVCAF 208
Cdd:cd05332  87 NNAGIS---MRSLFHDTSIDVdRKIMEVNYFGPVALTKAALPHLIERSQGSIVVVSSIAGKIGVPFRTAYAASKHALQGF 163

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4557649  209 SKALQEEYKAKEVIIQVLTPYAVSTAMTKYLNTNVITKTADEFVKESLNYVTiggETCgclAHEILAG--------FLSL 280
Cdd:cd05332 164 FDSLRAELSEPNISVTVVCPGLIDTNIAMNALSGDGSMSAKMDDTTANGMSP---EEC---ALEILKAialrkrevFYAR 237

                ....*..
gi 4557649  281 IPAWAFY 287
Cdd:cd05332 238 QVPLLAV 244

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 4557649   51 AVITGAGDGIGKAYSFELAKRGLNVVLISRTLEKLEAIAT-EIERTTgrSVKIIQADFTKDD----IYEHIKEKLAGLEI 125
Cdd:cd05323   3 AIITGGASGIGLATAKLLLKKGAKVAILDRNENPGAAAELqAINPKV--KATFVQCDVTSWEqlaaAFKKAIEKFGRVDI 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4557649  126 giLVNNVGMLPNLLPSHFLNAPDEIQSLIHCNITSVVKMTQLILKHMESRQK---GLILNISSGIALFPWPLYSMYSASK 202
Cdd:cd05323  81 --LINNAGILDEKSYLFAGKLPPPWEKTIDVNLTGVINTTYLALHYMDKNKGgkgGVIVNIGSVAGLYPAPQFPVYSASK 158

                       170       180       190       200
                ....*....|....*....|....*....|....*....|..
gi 4557649  203 AFVCAFSKALQEEYKAKE-VIIQVLTPYAVSTAMTKYLNTNV 243
Cdd:cd05323 159 HGVVGFTRSLADLLEYKTgVRVNAICPGFTNTPLLPDLVAKE 200

beta-Keto acyl carrier protein reductase (BKR), involved in Type II FAS, classical (c) SDRs; This subgroup includes the Escherichai coli K12 BKR, FabG. BKR catalyzes the NADPH-dependent reduction of ACP in the first reductive step of de novo fatty acid synthesis (FAS). FAS consists of four elongation steps, which are repeated to extend the fatty acid chain through the addition of two-carbo units from malonyl acyl-carrier protein (ACP): condensation, reduction, dehydration, and a final reduction. Type II FAS, typical of plants and many bacteria, maintains these activities on discrete polypeptides, while type I FAS utilizes one or two multifunctional polypeptides. BKR resembles enoyl reductase, which catalyzes the second reduction step in FAS. SDRs are a functionally diverse family of oxidoreductases that have a single domain with structurally conserved Rossmann fold (alpha/beta folding pattern with a central beta-sheet) 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: TGxxxGxG in classical SDRs. 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 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. 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-151 and Lys-155, and well as Asn-111 (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 4557649   51 AVITGAGDGIGKAYSFELAKRGLNVVLISRTLEKLEAIATEIERtTGRSVKIIQADFTK----DDIYEHIKEKLAGLEig 126
Cdd:cd05333   3 ALVTGASRGIGRAIALRLAAEGAKVAVTDRSEEAAAETVEEIKA-LGGNAAALEADVSDreavEALVEKVEAEFGPVD-- 79

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4557649  127 ILVNNVG-----MLPNLlpshflnAPDEIQSLIHCNITSVVKMTQLILKHMESRQKGLILNISSGIALFPWPLYSMYSAS 201
Cdd:cd05333  80 ILVNNAGitrdnLLMRM-------SEEDWDAVINVNLTGVFNVTQAVIRAMIKRRSGRIINISSVVGLIGNPGQANYAAS 152

                       170       180       190       200
                ....*....|....*....|....*....|....*....|....*
gi 4557649  202 KAFVCAFSKALQEEYKAKEVIIQVLTPYAVSTAMTKYLNTNVITK 246
Cdd:cd05333 153 KAGVIGFTKSLAKELASRGITVNAVAPGFIDTDMTDALPEKVKEK 197

gluconate 5-dehydrogenase (Ga5DH)-like, classical (c) SDRs; Ga5DH catalyzes the NADP-dependent conversion of carbon source D-gluconate and 5-keto-D-gluconate. This SDR subgroup has a classical Gly-rich NAD(P)-binding motif and a conserved active site tetrad pattern. However, it has been proposed that Arg104 (Streptococcus suis Ga5DH numbering), as well as an active site Ca2+, play a critical role in catalysis. In addition to Ga5DHs this subgroup contains Erwinia chrysanthemi KduD which is involved in pectin degradation, and is a putative 2,5-diketo-3-deoxygluconate dehydrogenase. 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 4557649   48 GQWAVITGAGDGIGKAYSFELAKRGLNVVLISRTLEKLEAIATEIERtTGRSVKIIQADFTKDD----IYEHIKEKLAgl 123
Cdd:cd05347   5 GKVALVTGASRGIGFGIASGLAEAGANIVINSRNEEKAEEAQQLIEK-EGVEATAFTCDVSDEEaikaAVEAIEEDFG-- 81

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4557649  124 EIGILVNNVGMlpnLLPSHFLNAPDE-IQSLIHCNITSVVKMTQLILKHMESRQKGLILNISSGIALFPWPLYSMYSASK 202
Cdd:cd05347  82 KIDILVNNAGI---IRRHPAEEFPEAeWRDVIDVNLNGVFFVSQAVARHMIKQGHGKIINICSLLSELGGPPVPAYAASK 158

                       170       180       190
                ....*....|....*....|....*....|....*
gi 4557649  203 AFVCAFSKALQEEYKAKEVIIQVLTPYAVSTAMTK 237
Cdd:cd05347 159 GGVAGLTKALATEWARHGIQVNAIAPGYFATEMTE 193