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 568983060  86 GQWAVITGAGDGIGKAYSFELARHGLNVVLISRTLEKLQTIAEEIERTTGSCVKIVQADFT-REDIYDHIKEHLEGLEIG 164
Cdd:cd05356    1 GTWAVVTGATDGIGKAYAEELAKRGFNVILISRTQEKLDAVAKEIEEKYGVETKTIAADFSaGDDIYERIEKELEGLDIG 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568983060 165 ILVNNVGMLPSFfPSHFLSTSGES-QNLIHCNITSVVKMTQLVLKHMESRRKGLILNISSGAALRPWPLYSLYSASKAFV 243
Cdd:cd05356   81 ILVNNVGISHSI-PEYFLETPEDElQDIINVNVMATLKMTRLILPGMVKRKKGAIVNISSFAGLIPTPLLATYSASKAFL 159

                        170       180       190
                 ....*....|....*....|....*....|
gi 568983060 244 YTFSKALSVEYRDKGIIIQV-----VHVKM 268
Cdd:cd05356  160 DFFSRALYEEYKSQGIDVQSllpylVATKM 189

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 568983060  86 GQWAVITGAGDGIGKAYSFELARHGLNVVLISRTLEKLQTIAEEIERTTGSCVKIVQADFT-REDIYDHIKEHLEGLEIG 164
Cdd:cd05356    1 GTWAVVTGATDGIGKAYAEELAKRGFNVILISRTQEKLDAVAKEIEEKYGVETKTIAADFSaGDDIYERIEKELEGLDIG 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568983060 165 ILVNNVGMLPSFfPSHFLSTSGES-QNLIHCNITSVVKMTQLVLKHMESRRKGLILNISSGAALRPWPLYSLYSASKAFV 243
Cdd:cd05356   81 ILVNNVGISHSI-PEYFLETPEDElQDIINVNVMATLKMTRLILPGMVKRKKGAIVNISSFAGLIPTPLLATYSASKAFL 159

                        170       180       190
                 ....*....|....*....|....*....|
gi 568983060 244 YTFSKALSVEYRDKGIIIQV-----VHVKM 268
Cdd:cd05356  160 DFFSRALYEEYKSQGIDVQSllpylVATKM 189

Short-chain dehydrogenase [General function prediction only];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568983060  85 MGQWAVITGAGDGIGKAYSFELARHGLNVVLISRTLEKLQTIAEEIeRTTGSCVKIVQADFTRED----IYDHIKEHLEG 160
Cdd:COG0300    4 TGKTVLITGASSGIGRALARALAARGARVVLVARDAERLEALAAEL-RAAGARVEVVALDVTDPDavaaLAEAVLARFGP 82

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568983060 161 leIGILVNNVGMLPsffPSHFLSTSGES-QNLIHCNITSVVKMTQLVLKHMESRRKGLILNISSGAALRPWPLYSLYSAS 239
Cdd:COG0300   83 --IDVLVNNAGVGG---GGPFEELDLEDlRRVFEVNVFGPVRLTRALLPLMRARGRGRIVNVSSVAGLRGLPGMAAYAAS 157

                        170       180       190
                 ....*....|....*....|....*....|..
gi 568983060 240 KAFVYTFSKALSVEYRDKGIIIQVVHvkMGWT 271
Cdd:COG0300  158 KAALEGFSESLRAELAPTGVRVTAVC--PGPV 187

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 568983060   89 AVITGAGDGIGKAYSFELAR----HGLNVVLISRTLEKLQTIAEEIERTT-GSCVKIVQADFTRE-DIYDHIKEHLE--- 159
Cdd:TIGR01500   3 CLVTGASRGFGRTIAQELAKclksPGSVLVLSARNDEALRQLKAEIGAERsGLRVVRVSLDLGAEaGLEQLLKALRElpr 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568983060  160 --GLEIGILVNNVGMLPSFFP-SHFLSTSGESQNLIHCNITSVVKMTQLVLKHMESRR--KGLILNISSGAALRPWPLYS 234
Cdd:TIGR01500  83 pkGLQRLLLINNAGTLGDVSKgFVDLSDSTQVQNYWALNLTSMLCLTSSVLKAFKDSPglNRTVVNISSLCAIQPFKGWA 162

                         170       180
                  ....*....|....*....|.
gi 568983060  235 LYSASKAFVYTFSKALSVEYR 255
Cdd:TIGR01500 163 LYCAGKAARDMLFQVLALEEK 183

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 568983060  86 GQWAVITGAGDGIGKAYSFELARHGLNVVLISRTLEKLQTIAEEIERTTGSCVKIVQADFT-REDIYDHIKEHLEGLEIG 164
Cdd:cd05356    1 GTWAVVTGATDGIGKAYAEELAKRGFNVILISRTQEKLDAVAKEIEEKYGVETKTIAADFSaGDDIYERIEKELEGLDIG 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568983060 165 ILVNNVGMLPSFfPSHFLSTSGES-QNLIHCNITSVVKMTQLVLKHMESRRKGLILNISSGAALRPWPLYSLYSASKAFV 243
Cdd:cd05356   81 ILVNNVGISHSI-PEYFLETPEDElQDIINVNVMATLKMTRLILPGMVKRKKGAIVNISSFAGLIPTPLLATYSASKAFL 159

                        170       180       190
                 ....*....|....*....|....*....|
gi 568983060 244 YTFSKALSVEYRDKGIIIQV-----VHVKM 268
Cdd:cd05356  160 DFFSRALYEEYKSQGIDVQSllpylVATKM 189

Short-chain dehydrogenase [General function prediction only];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568983060  85 MGQWAVITGAGDGIGKAYSFELARHGLNVVLISRTLEKLQTIAEEIeRTTGSCVKIVQADFTRED----IYDHIKEHLEG 160
Cdd:COG0300    4 TGKTVLITGASSGIGRALARALAARGARVVLVARDAERLEALAAEL-RAAGARVEVVALDVTDPDavaaLAEAVLARFGP 82

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568983060 161 leIGILVNNVGMLPsffPSHFLSTSGES-QNLIHCNITSVVKMTQLVLKHMESRRKGLILNISSGAALRPWPLYSLYSAS 239
Cdd:COG0300   83 --IDVLVNNAGVGG---GGPFEELDLEDlRRVFEVNVFGPVRLTRALLPLMRARGRGRIVNVSSVAGLRGLPGMAAYAAS 157

                        170       180       190
                 ....*....|....*....|....*....|..
gi 568983060 240 KAFVYTFSKALSVEYRDKGIIIQVVHvkMGWT 271
Cdd:COG0300  158 KAALEGFSESLRAELAPTGVRVTAVC--PGPV 187

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 568983060  89 AVITGAGDGIGKAYSFELARHGLNVVLISRTLEKLQTIAEEIERttGSCVKIVQADFTRED----IYDHIKEHLEGleIG 164
Cdd:cd05233    1 ALVTGASSGIGRAIARRLAREGAKVVLADRNEEALAELAAIEAL--GGNAVAVQADVSDEEdveaLVEEALEEFGR--LD 76

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568983060 165 ILVNNVGMLPSFFPSHFlsTSGESQNLIHCNITSVVKMTQLVLKHMESRRKGLILNISSGAALRPWPLYSLYSASKAFVY 244
Cdd:cd05233   77 ILVNNAGIARPGPLEEL--TDEDWDRVLDVNLTGVFLLTRAALPHMKKQGGGRIVNISSVAGLRPLPGQAAYAASKAALE 154

                        170       180       190
                 ....*....|....*....|....*....|....*...
gi 568983060 245 TFSKALSVEYRDKGIIIQVVHVKMGWTGLLGSPDQDQA 282
Cdd:cd05233  155 GLTRSLALELAPYGIRVNAVAPGLVDTPMLAKLGPEEA 192

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 568983060  86 GQWAVITGAGDGIGKAYSFELARHGLNVVLISRTLEKLQTIAEEIerttGSCVKIVQADFTRED----IYDHIKEHLEGL 161
Cdd:COG4221    5 GKVALITGASSGIGAATARALAAAGARVVLAARRAERLEALAAEL----GGRALAVPLDVTDEAaveaAVAAAVAEFGRL 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568983060 162 EIgiLVNNVGMLPsffPSHFLSTSGES-QNLIHCNITSVVKMTQLVLKHMESRRKGLILNISSGAALRPWPLYSLYSASK 240
Cdd:COG4221   81 DV--LVNNAGVAL---LGPLEELDPEDwDRMIDVNVKGVLYVTRAALPAMRARGSGHIVNISSIAGLRPYPGGAVYAATK 155

                        170       180       190
                 ....*....|....*....|....*....|....*.
gi 568983060 241 AFVYTFSKALSVEYRDKGIIIQVVHVKMGWTGLLGS 276
Cdd:COG4221  156 AAVRGLSESLRAELRPTGIRVTVIEPGAVDTEFLDS 191

3-ketoacyl-(acyl-carrier-protein) reductase; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568983060  86 GQWAVITGAGDGIGKAYSFELARHGLNVVLISRTLEKLQTIAEEIERtTGSCVKIVQADFTREDIYDHIKEHLEGL--EI 163
Cdd:PRK07666   7 GKNALITGAGRGIGRAVAIALAKEGVNVGLLARTEENLKAVAEEVEA-YGVKVVIATADVSDYEEVTAAIEQLKNElgSI 85

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568983060 164 GILVNNVGMlpSFFPSHFLSTSGESQNLIHCNITSVVKMTQLVLKHMESRRKGLILNISSGAALRPWPLYSLYSASKAFV 243
Cdd:PRK07666  86 DILINNAGI--SKFGKFLELDPAEWEKIIQVNLMGVYYATRAVLPSMIERQSGDIINISSTAGQKGAAVTSAYSASKFGV 163

                        170
                 ....*....|....*.
gi 568983060 244 YTFSKALSVEYRDKGI 259
Cdd:PRK07666 164 LGLTESLMQEVRKHNI 179

3-ketoacyl-(acyl-carrier-protein) reductase; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568983060  83 RSMGQWAVITGAGDGIGKAYSFELARHGLNVVLISRT-LEKLQTIAEEIERTTGSCVkIVQADFTRED----IYDHIKEH 157
Cdd:PRK05565   2 KLMGKVAIVTGASGGIGRAIAELLAKEGAKVVIAYDInEEAAQELLEEIKEEGGDAI-AVKADVSSEEdvenLVEQIVEK 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568983060 158 LEGLEigILVNNVGMlpSFFPSHFLSTSGESQNLIHCNITSVVKMTQLVLKHMESRRKGLILNISSGAALRPWPLYSLYS 237
Cdd:PRK05565  81 FGKID--ILVNNAGI--SNFGLVTDMTDEEWDRVIDVNLTGVMLLTRYALPYMIKRKSGVIVNISSIWGLIGASCEVLYS 156

                        170       180       190
                 ....*....|....*....|....*....|...
gi 568983060 238 ASKAFVYTFSKALSVEYRDKGiiIQVVHVKMGW 270
Cdd:PRK05565 157 ASKGAVNAFTKALAKELAPSG--IRVNAVAPGA 187

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 568983060  90 VITGAGDGIGKAYSFELARHGLNVVLISRTLEKLQTIAEEIERTTGSCVKIVQADFTR-EDIYDHIKEHLEGL-EIGILV 167
Cdd:cd05332    7 IITGASSGIGEELAYHLARLGARLVLSARREERLEEVKSECLELGAPSPHVVPLDMSDlEDAEQVVEEALKLFgGLDILI 86

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568983060 168 NNVGMlpsFFPSHFLSTSGES-QNLIHCNITSVVKMTQLVLKHMESRRKGLILNISSGAALRPWPLYSLYSASKAFVYTF 246
Cdd:cd05332   87 NNAGI---SMRSLFHDTSIDVdRKIMEVNYFGPVALTKAALPHLIERSQGSIVVVSSIAGKIGVPFRTAYAASKHALQGF 163

                        170
                 ....*....|....*...
gi 568983060 247 SKALSVEYRDKGIIIQVV 264
Cdd:cd05332  164 FDSLRAELSEPNISVTVV 181

3-oxoacyl-ACP reductase FabG;

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568983060  85 MGQWAVITGAGDGIGKAYSFELARHGLNVVLISRTLEKLQTIAEEIERTTGSCVkIVQADFTRED----IYDHIKEHLEG 160
Cdd:PRK05653   4 QGKTALVTGASRGIGRAIALRLAADGAKVVIYDSNEEAAEALAAELRAAGGEAR-VLVFDVSDEAavraLIEAAVEAFGA 82

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568983060 161 LEigILVNNVGMLPsFFPSHFLSTSgESQNLIHCNITSVVKMTQLVLKHMESRRKGLILNISSGAALRPWPLYSLYSASK 240
Cdd:PRK05653  83 LD--ILVNNAGITR-DALLPRMSEE-DWDRVIDVNLTGTFNVVRAALPPMIKARYGRIVNISSVSGVTGNPGQTNYSAAK 158

                        170
                 ....*....|....*....
gi 568983060 241 AFVYTFSKALSVEYRDKGI 259
Cdd:PRK05653 159 AGVIGFTKALALELASRGI 177

glucose 1 dehydrogenase (GlcDH), classical (c) SDRs; GlcDH, is a tetrameric member of the SDR family, it catalyzes the NAD(P)-dependent oxidation of beta-D-glucose to D-glucono-delta-lactone. GlcDH has a typical NAD-binding site glycine-rich pattern as well as the canonical active site tetrad (YXXXK motif plus upstream Ser and Asn). 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 568983060  86 GQWAVITGAGDGIGKAYSFELARHGLNVVLISRT-LEKLQTIAEEIERTTGSCVkIVQADFTRED----IYDHIKEHLEG 160
Cdd:cd05358    3 GKVALVTGASSGIGKAIAIRLATAGANVVVNYRSkEDAAEEVVEEIKAVGGKAI-AVQADVSKEEdvvaLFQSAIKEFGT 81

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568983060 161 LEIgiLVNNVGMLPSFfPSHFLSTSgESQNLIHCNITSVVKMTQLVLKHM-ESRRKGLILNISSGAALRPWPLYSLYSAS 239
Cdd:cd05358   82 LDI--LVNNAGLQGDA-SSHEMTLE-DWNKVIDVNLTGQFLCAREAIKRFrKSKIKGKIINMSSVHEKIPWPGHVNYAAS 157

                        170       180
                 ....*....|....*....|
gi 568983060 240 KAFVYTFSKALSVEYRDKGI 259
Cdd:cd05358  158 KGGVKMMTKTLAQEYAPKGI 177

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 568983060  89 AVITGAGDGIGKAYSFELARHGLNVVLISRTLEKLQTIAEEIERtTGSCVKIVQADFT-REDIYDHIKEHLEGL-EIGIL 166
Cdd:cd05333    3 ALVTGASRGIGRAIALRLAAEGAKVAVTDRSEEAAAETVEEIKA-LGGNAAALEADVSdREAVEALVEKVEAEFgPVDIL 81

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568983060 167 VNNVG-----MLPSFFPSHFlstsgesQNLIHCNITSVVKMTQLVLKHMESRRKGLILNISSGAALRPWPLYSLYSASKA 241
Cdd:cd05333   82 VNNAGitrdnLLMRMSEEDW-------DAVINVNLTGVFNVTQAVIRAMIKRRSGRIINISSVVGLIGNPGQANYAASKA 154

                        170       180
                 ....*....|....*....|...
gi 568983060 242 FVYTFSKALSVEYRDKGIIIQVV 264
Cdd:cd05333  155 GVIGFTKSLAKELASRGITVNAV 177

17beta hydroxysteroid dehydrogenase-like, classical (c) SDRs; 17beta-hydroxysteroid dehydrogenases are a group of isozymes that catalyze activation and inactivation of estrogen and androgens. 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 568983060  89 AVITGAGDGIGKAYSFELARHGLNVVLISRTLEKLQTIAEEiertTGSCVKIVQADFTRED-IYDHIKEHLE-GLEIGIL 166
Cdd:cd05374    3 VLITGCSSGIGLALALALAAQGYRVIATARNPDKLESLGEL----LNDNLEVLELDVTDEEsIKAAVKEVIErFGRIDVL 78

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568983060 167 VNNVGMlPSFFPshFLSTSGES-QNLIHCNITSVVKMTQLVLKHMESRRKGLILNISSGAALRPWPLYSLYSASKAFVYT 245
Cdd:cd05374   79 VNNAGY-GLFGP--LEETSIEEvRELFEVNVFGPLRVTRAFLPLMRKQGSGRIVNVSSVAGLVPTPFLGPYCASKAALEA 155

                        170
                 ....*....|....*....
gi 568983060 246 FSKALSVEYRDKGiiIQVV 264
Cdd:cd05374  156 LSESLRLELAPFG--IKVT 172

putative beta-ketoacyl acyl carrier protein [ACP] reductase (BKR), subgroup 3, classical (c) SDR; This subgroup includes the putative Brucella melitensis biovar Abortus 2308 BKR, FabG, Mesorhizobium loti MAFF303099 FabG, and other classical SDRs. BKR, a member of the SDR family, catalyzes the NADPH-dependent reduction of acyl carrier protein in the first reductive step of de novo fatty acid synthesis (FAS). FAS consists of 4 elongation steps, which are repeated to extend the fatty acid chain thru the addition of two-carbo units from malonyl acyl-carrier protein (ACP): condensation, reduction, dehydration, and final reduction. Type II FAS, typical of plants and many bacteria, maintains these activities on discrete polypeptides, while type I Fas utilizes one or 2 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 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 568983060  83 RSMGQWAVITGAGDGIGKAYSFELARHGLNVVLISRTLEKLQTIAEEIerttGSCVKIVQADFTREDIYDHIKEHL--EG 160
Cdd:cd05345    2 RLEGKVAIVTGAGSGFGEGIARRFAQEGARVVIADINADGAERVAADI----GEAAIAIQADVTKRADVEAMVEAAlsKF 77

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568983060 161 LEIGILVNNVGMlpSFFPSHFLSTSGESQNLI-HCNITSVVKMTQLVLKHMESRRKGLILNISSGAALRPWPLYSLYSAS 239
Cdd:cd05345   78 GRLDILVNNAGI--THRNKPMLEVDEEEFDRVfAVNVKSIYLSAQALVPHMEEQGGGVIINIASTAGLRPRPGLTWYNAS 155

                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568983060 240 KAFVYTFSKALSVEYRDKGIIIQVVHVKMGWTGLL---GSPD--------------------QDQANCCL 286
Cdd:cd05345  156 KGWVVTATKAMAVELAPRNIRVNCLCPVAGETPLLsmfMGEDtpenrakfratiplgrlstpDDIANAAL 225

Enoyl-(Acyl carrier protein) reductase; This domain is found in Enoyl-(Acyl carrier protein) reductases.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568983060   97 GIGKAYSFELARHGLNVVLISRTlEKLQTIAEEIERTTGScvKIVQADFTRED----IYDHIKEHLEGLEIgiLVNNVGM 172
Cdd:pfam13561   7 GIGWAIARALAEEGAEVVLTDLN-EALAKRVEELAEELGA--AVLPCDVTDEEqveaLVAAAVEKFGRLDI--LVNNAGF 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568983060  173 LPSFFpSHFLSTSGES-QNLIHCNITSVVKMTQLVLKHMesRRKGLILNISSGAALRPWPLYSLYSASKAFVYTFSKALS 251
Cdd:pfam13561  82 APKLK-GPFLDTSREDfDRALDVNLYSLFLLAKAALPLM--KEGGSIVNLSSIGAERVVPNYNAYGAAKAALEALTRYLA 158

                  ....*...
gi 568983060  252 VEYRDKGI 259
Cdd:pfam13561 159 VELGPRGI 166

1-cyclohexenylcarbonyl_coenzyme A_reductase (ChcA)_like, classical (c) SDRs; This subgroup contains classical SDR proteins, including members identified as 1-cyclohexenylcarbonyl coenzyme A reductase. ChcA of Streptomyces collinus is implicated in the final reduction step of shikimic acid to ansatrienin. ChcA shows sequence similarity to the SDR family of NAD-binding proteins, but it lacks the conserved Tyr of the characteristic catalytic site. This subgroup also contains the NADH-dependent enoyl-[acyl-carrier-protein(ACP)] reductase FabL from Bacillus subtilis. This enzyme participates in bacterial fatty acid synthesis, in type II fatty-acid synthases and catalyzes the last step in each elongation cycle. 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 568983060  89 AVITGAGDGIGKAYSFELARHGLNVVLISR-TLEKLQTIAEEIERTTGSCVkIVQADFTR----EDIYDHIKEHLEGLEI 163
Cdd:cd05359    1 ALVTGGSRGIGKAIALRLAERGADVVINYRkSKDAAAEVAAEIEELGGKAV-VVRADVSQpqdvEEMFAAVKERFGRLDV 79

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568983060 164 giLVNNVGmlPSFF-------PSHF-LSTSGESQNLIHCnitsvvkmTQLVLKHMESRRKGLILNISSGAALRPWPLYSL 235
Cdd:cd05359   80 --LVSNAA--AGAFrplseltPAHWdAKMNTNLKALVHC--------AQQAAKLMRERGGGRIVAISSLGSIRALPNYLA 147