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 121802247  67 GSWAVVTGASDGLGKEFSLQLARAGFNIVLVSRTASKLTTLSDEITSKYaSVQTKTLAMDFArNEDSDYEKLKALVDELD 146
Cdd:cd05356    1 GTWAVVTGATDGIGKAYAEELAKRGFNVILISRTQEKLDAVAKEIEEKY-GVETKTIAADFS-AGDDIYERIEKELEGLD 78

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 121802247 147 VAILVNNVGKSHDIPTPFALTSQEEMTDIITINCMGTLRATQLIVPGMMQRKRGLILTMGSFGGLLPTPLLATYSGSKAF 226
Cdd:cd05356   79 IGILVNNVGISHSIPEYFLETPEDELQDIINVNVMATLKMTRLILPGMVKRKKGAIVNISSFAGLIPTPLLATYSASKAF 158

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 121802247 227 LQQWSTALGSELEEHGITVELVQAYLITSAMSKIRRASATIPDPRSFVKSVLSKIGRN 284
Cdd:cd05356  159 LDFFSRALYEEYKSQGIDVQSLLPYLVATKMSKIRKSSLFVPSPEQFVRSALNTLGLS 216

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 121802247  67 GSWAVVTGASDGLGKEFSLQLARAGFNIVLVSRTASKLTTLSDEITSKYaSVQTKTLAMDFArNEDSDYEKLKALVDELD 146
Cdd:cd05356    1 GTWAVVTGATDGIGKAYAEELAKRGFNVILISRTQEKLDAVAKEIEEKY-GVETKTIAADFS-AGDDIYERIEKELEGLD 78

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 121802247 147 VAILVNNVGKSHDIPTPFALTSQEEMTDIITINCMGTLRATQLIVPGMMQRKRGLILTMGSFGGLLPTPLLATYSGSKAF 226
Cdd:cd05356   79 IGILVNNVGISHSIPEYFLETPEDELQDIINVNVMATLKMTRLILPGMVKRKKGAIVNISSFAGLIPTPLLATYSASKAF 158

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 121802247 227 LQQWSTALGSELEEHGITVELVQAYLITSAMSKIRRASATIPDPRSFVKSVLSKIGRN 284
Cdd:cd05356  159 LDFFSRALYEEYKSQGIDVQSLLPYLVATKMSKIRKSSLFVPSPEQFVRSALNTLGLS 216

Short-chain dehydrogenase [General function prediction only];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 121802247  66 KGSWAVVTGASDGLGKEFSLQLARAGFNIVLVSRTASKLTTLSDEITSKYASVQTktLAMDFarnedSDYEKLKALVDEL 145
Cdd:COG0300    4 TGKTVLITGASSGIGRALARALAARGARVVLVARDAERLEALAAELRAAGARVEV--VALDV-----TDPDAVAALAEAV 76

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 121802247 146 -----DVAILVNNVGKSHdiPTPFALTSQEEMTDIITINCMGTLRATQLIVPGMMQRKRGLILTMGSFGGLLPTPLLATY 220
Cdd:COG0300   77 larfgPIDVLVNNAGVGG--GGPFEELDLEDLRRVFEVNVFGPVRLTRALLPLMRARGRGRIVNVSSVAGLRGLPGMAAY 154

                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 121802247 221 SGSKAFLQQWSTALGSELEEHGITVELVQAYLITSAMSKIRRASATIP--DPRSFVKSVLSKIGRN 284
Cdd:COG0300  155 AASKAALEGFSESLRAELAPTGVRVTAVCPGPVDTPFTARAGAPAGRPllSPEEVARAILRALERG 220

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 121802247   70 AVVTGASDGLGKEFSLQLARA----GFNIVLVSRTASKLTTLSDEITSKYA--SVQTKTLAMDFARNEDSDYEKLKALV- 142
Cdd:TIGR01500   3 CLVTGASRGFGRTIAQELAKClkspGSVLVLSARNDEALRQLKAEIGAERSglRVVRVSLDLGAEAGLEQLLKALRELPr 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 121802247  143 -DELDVAILVNNVGKSHDIPTPFaltsqEEMTDIITINCMGTLRATQLIVPG--------MMQRKRGLILTMGSFGGLLP 213
Cdd:TIGR01500  83 pKGLQRLLLINNAGTLGDVSKGF-----VDLSDSTQVQNYWALNLTSMLCLTssvlkafkDSPGLNRTVVNISSLCAIQP 157

                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 121802247  214 TPLLATYSGSKAFLQQWSTALGSELEEHGITVELVQAYLITSAMSKIRRASATIPDPRSF 273
Cdd:TIGR01500 158 FKGWALYCAGKAARDMLFQVLALEEKNPNVRVLNYAPGVLDTDMQQQVREESVDPDMRKG 217

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 121802247  67 GSWAVVTGASDGLGKEFSLQLARAGFNIVLVSRTASKLTTLSDEITSKYaSVQTKTLAMDFArNEDSDYEKLKALVDELD 146
Cdd:cd05356    1 GTWAVVTGATDGIGKAYAEELAKRGFNVILISRTQEKLDAVAKEIEEKY-GVETKTIAADFS-AGDDIYERIEKELEGLD 78

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 121802247 147 VAILVNNVGKSHDIPTPFALTSQEEMTDIITINCMGTLRATQLIVPGMMQRKRGLILTMGSFGGLLPTPLLATYSGSKAF 226
Cdd:cd05356   79 IGILVNNVGISHSIPEYFLETPEDELQDIINVNVMATLKMTRLILPGMVKRKKGAIVNISSFAGLIPTPLLATYSASKAF 158

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 121802247 227 LQQWSTALGSELEEHGITVELVQAYLITSAMSKIRRASATIPDPRSFVKSVLSKIGRN 284
Cdd:cd05356  159 LDFFSRALYEEYKSQGIDVQSLLPYLVATKMSKIRKSSLFVPSPEQFVRSALNTLGLS 216

Short-chain dehydrogenase [General function prediction only];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 121802247  66 KGSWAVVTGASDGLGKEFSLQLARAGFNIVLVSRTASKLTTLSDEITSKYASVQTktLAMDFarnedSDYEKLKALVDEL 145
Cdd:COG0300    4 TGKTVLITGASSGIGRALARALAARGARVVLVARDAERLEALAAELRAAGARVEV--VALDV-----TDPDAVAALAEAV 76

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 121802247 146 -----DVAILVNNVGKSHdiPTPFALTSQEEMTDIITINCMGTLRATQLIVPGMMQRKRGLILTMGSFGGLLPTPLLATY 220
Cdd:COG0300   77 larfgPIDVLVNNAGVGG--GGPFEELDLEDLRRVFEVNVFGPVRLTRALLPLMRARGRGRIVNVSSVAGLRGLPGMAAY 154

                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 121802247 221 SGSKAFLQQWSTALGSELEEHGITVELVQAYLITSAMSKIRRASATIP--DPRSFVKSVLSKIGRN 284
Cdd:COG0300  155 AASKAALEGFSESLRAELAPTGVRVTAVCPGPVDTPFTARAGAPAGRPllSPEEVARAILRALERG 220

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 121802247  66 KGSWAVVTGASDGLGKEFSLQLARAGFNIVLVSRTASKLTTLSDEItskyaSVQTKTLAMDFarnedSDYEKLKALVDEL 145
Cdd:COG4221    4 KGKVALITGASSGIGAATARALAAAGARVVLAARRAERLEALAAEL-----GGRALAVPLDV-----TDEAAVEAAVAAA 73

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 121802247 146 D-----VAILVNNVGksHDIPTPFALTSQEEMTDIITINCMGTLRATQLIVPGMMQRKRGLILTMGSFGGLLPTPLLATY 220
Cdd:COG4221   74 VaefgrLDVLVNNAG--VALLGPLEELDPEDWDRMIDVNVKGVLYVTRAALPAMRARGSGHIVNISSIAGLRPYPGGAVY 151

                        170       180
                 ....*....|....*....|....*
gi 121802247 221 SGSKAFLQQWSTALGSELEEHGITV 245
Cdd:COG4221  152 AATKAAVRGLSESLRAELRPTGIRV 176

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 121802247  70 AVVTGASDGLGKEFSLQLARAGFNIVLVSRTASKLTTLSDEitsKYASVQTKTLAMDfarneDSDYEKLKALVDELDVA- 148
Cdd:cd05233    1 ALVTGASSGIGRAIARRLAREGAKVVLADRNEEALAELAAI---EALGGNAVAVQAD-----VSDEEDVEALVEEALEEf 72

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 121802247 149 ----ILVNNVGKSHdiPTPFALTSQEEMTDIITINCMGTLRATQLIVPGMMQRKRGLILTMGSFGGLLPTPLLATYSGSK 224
Cdd:cd05233   73 grldILVNNAGIAR--PGPLEELTDEDWDRVLDVNLTGVFLLTRAALPHMKKQGGGRIVNISSVAGLRPLPGQAAYAASK 150

                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 121802247 225 AFLQQWSTALGSELEEHGITVELVQAYLITSAMskirrASATIPDPRSFVKSVLSKIGRNG 285
Cdd:cd05233  151 AALEGLTRSLALELAPYGIRVNAVAPGLVDTPM-----LAKLGPEEAEKELAAAIPLGRLG 206

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 121802247  70 AVVTGASDGLGKEFSLQLARAGFNIVLVSRTASKLTTLSDEITSKYaSVQTKTLAMDFarnedSDYEKLKALVDEL---- 145
Cdd:cd05346    3 VLITGASSGIGEATARRFAKAGAKLILTGRRAERLQELADELGAKF-PVKVLPLQLDV-----SDRESIEAALENLpeef 76

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 121802247 146 -DVAILVNNVGKSHDIPtPFALTSQEEMTDIITINCMGTLRATQLIVPGMMQRKRGLILTMGSFGGLLPTPLLATYSGSK 224
Cdd:cd05346   77 rDIDILVNNAGLALGLD-PAQEADLEDWETMIDTNVKGLLNVTRLILPIMIARNQGHIINLGSIAGRYPYAGGNVYCATK 155

                        170       180       190
                 ....*....|....*....|....*....|....*..
gi 121802247 225 AFLQQWSTALGSELEEHGITVELVQAYLITSAMSKIR 261
Cdd:cd05346  156 AAVRQFSLNLRKDLIGTGIRVTNIEPGLVETEFSLVR 192

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 121802247  71 VVTGASDGLGKEFSLQLARAGFNIVLVSRTASKLTTLSDEITSKYAsVQTKTLAMDFarnedSDYEKLKALVDE------ 144
Cdd:cd05332    7 IITGASSGIGEELAYHLARLGARLVLSARREERLEEVKSECLELGA-PSPHVVPLDM-----SDLEDAEQVVEEalklfg 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 121802247 145 -LDvaILVNNVGKShdIPTPFALTSQEEMTDIITINCMGTLRATQLIVPGMMQRKRGLILTMGSFGGLLPTPLLATYSGS 223
Cdd:cd05332   81 gLD--ILINNAGIS--MRSLFHDTSIDVDRKIMEVNYFGPVALTKAALPHLIERSQGSIVVVSSIAGKIGVPFRTAYAAS 156

                        170       180
                 ....*....|....*....|....*
gi 121802247 224 KAFLQQWSTALGSELEEHGITVELV 248
Cdd:cd05332  157 KHALQGFFDSLRAELSEPNISVTVV 181

human 17-beta-hydroxysteroid dehydrogenase XI-like, classical (c) SDRs; 17-beta-hydroxysteroid dehydrogenases (17betaHSD) are a group of isozymes that catalyze activation and inactivation of estrogen and androgens. 17betaHSD type XI, a classical SDR, preferentially converts 3alpha-Adiol to androsterone but not numerous other tested steroids. This subgroup of classical SDRs also includes members identified as retinol dehydrogenases, which convert retinol to retinal, a property that overlaps with 17betaHSD activity. 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 121802247  70 AVVTGASDGLGKEFSLQLARAGFNIVLVSRTASKLTTLSDEItsKYASVQTKTLAMDFarnedSDYEKLKALVDEL---- 145
Cdd:cd05339    2 VLITGGGSGIGRLLALEFAKRGAKVVILDINEKGAEETANNV--RKAGGKVHYYKCDV-----SKREEVYEAAKKIkkev 74

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 121802247 146 -DVAILVNNVGkshdIPT--PFALTSQEEMTDIITINCMGTLRATQLIVPGMMQRKRGLILTMGSFGGLLPTPLLATYSG 222
Cdd:cd05339   75 gDVTILINNAG----VVSgkKLLELPDEEIEKTFEVNTLAHFWTTKAFLPDMLERNHGHIVTIASVAGLISPAGLADYCA 150

                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 121802247 223 SKAFLQQWSTALGSELEEH---GITVELVQAYLITSAM---SKIRRAS-ATIPDPRSFVKSVLSKIGRNGG 286
Cdd:cd05339  151 SKAAAVGFHESLRLELKAYgkpGIKTTLVCPYFINTGMfqgVKTPRPLlAPILEPEYVAEKIVRAILTNQQ 221

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 121802247  70 AVVTGASDGLGKEFSLQLARAGFNIVLVSRTASKLT-TLSDEITS---KYASVQTktlamDFarnedSDYEKLKALVDEL 145
Cdd:PRK05557   8 ALVTGASRGIGRAIAERLAAQGANVVINYASSEAGAeALVAEIGAlggKALAVQG-----DV-----SDAESVERAVDEA 77

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 121802247 146 -----DVAILVNNVGKSHDipTPFALTSQEEMTDIITINCMGTLRATQLIVPGMMQRKRGLILTMGSFGGLLPTPLLATY 220
Cdd:PRK05557  78 kaefgGVDILVNNAGITRD--NLLMRMKEEDWDRVIDTNLTGVFNLTKAVARPMMKQRSGRIINISSVVGLMGNPGQANY 155

                        170       180       190
                 ....*....|....*....|....*....|....*..
gi 121802247 221 SGSKAFLQQWSTALGSELEEHGITVELVQAYLITSAM 257
Cdd:PRK05557 156 AASKAGVIGFTKSLARELASRGITVNAVAPGFIETDM 192

SDR family oxidoreductase;

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 121802247  70 AVVTGASDGLGKEFSLQLARAGFNIVLVSRTASKLTTLSDEITS--KYASVQTKTlamdfarnedSDYEKLKALVDEL-- 145
Cdd:PRK07231   8 AIVTGASSGIGEGIARRFAAEGARVVVTDRNEEAAERVAAEILAggRAIAVAADV----------SDEADVEAAVAAAle 77

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 121802247 146 ---DVAILVNNVGKSHdIPTPFALTSQEEMTDIITINCMGTLRATQLIVPGMMQRKRGLILTMGSFGGLLPTPLLATYSG 222
Cdd:PRK07231  78 rfgSVDILVNNAGTTH-RNGPLLDVDEAEFDRIFAVNVKSPYLWTQAAVPAMRGEGGGAIVNVASTAGLRPRPGLGWYNA 156

                        170       180
                 ....*....|....*....|...
gi 121802247 223 SKAFLQQWSTALGSELEEHGITV 245
Cdd:PRK07231 157 SKGAVITLTKALAAELGPDKIRV 179

putative beta-ketoacyl acyl carrier protein [ACP] reductase (BKR)-like, SDR; This subgroup resembles the SDR family, but does not have a perfect match to the NAD-binding motif or the catalytic tetrad characteristic of the SDRs. It includes the SDRs, Q9HYA2 from Pseudomonas aeruginosa PAO1 and APE0912 from Aeropyrum pernix K1. 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 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 121802247  67 GSWAVVTGASDGLGKEFSLQLARAGFNIVLVSRTASKLTTLSDEITSKYASVqtKTLAMDFARNEDsdyekLKALVDELD 146
Cdd:cd05344    1 GKVALVTAASSGIGLAIARALAREGARVAICARNRENLERAASELRAGGAGV--LAVVADLTDPED-----IDRLVEKAG 73

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 121802247 147 -----VAILVNNVGksHDIPTPFALTSQEEMTDIITINCMGTLRATQLIVPGMMQRKRGLILTMGSFGGLLPTPLLATYS 221
Cdd:cd05344   74 dafgrVDILVNNAG--GPPPGPFAELTDEDWLEAFDLKLLSVIRIVRAVLPGMKERGWGRIVNISSLTVKEPEPNLVLSN 151

                        170       180
                 ....*....|....*....|....
gi 121802247 222 GSKAFLQQWSTALGSELEEHGITV 245
Cdd:cd05344  152 VARAGLIGLVKTLSRELAPDGVTV 175

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 121802247  63 FGPKGSWAVVTGASDGLGKEFSLQLARAGFNIVLVSRTASKLTTLSDEITSkyASVQTKTLAMDFarnedSDYEKLKALV 142
Cdd:cd05347    1 FSLKGKVALVTGASRGIGFGIASGLAEAGANIVINSRNEEKAEEAQQLIEK--EGVEATAFTCDV-----SDEEAIKAAV 73

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 121802247 143 DELD-----VAILVNNVGKSHdiPTPFALTSQEEMTDIITINCMGTLRATQLIVPGMMQRKRGLILTMGSFGGLLPTPLL 217
Cdd:cd05347   74 EAIEedfgkIDILVNNAGIIR--RHPAEEFPEAEWRDVIDVNLNGVFFVSQAVARHMIKQGHGKIINICSLLSELGGPPV 151

                        170       180
                 ....*....|....*....|....*...
gi 121802247 218 ATYSGSKAFLQQWSTALGSELEEHGITV 245
Cdd:cd05347  152 PAYAASKGGVAGLTKALATEWARHGIQV 179

short chain dehydrogenase; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 121802247  70 AVVTGASDGLGKEFSLQLARAGFNIVLVSRTASKLTTLSdeitskyasvQTKTLAMDfARNEDSdyekLKALVDEL---- 145
Cdd:PRK06179   7 ALVTGASSGIGRATAEKLARAGYRVFGTSRNPARAAPIP----------GVELLELD-VTDDAS----VQAAVDEViara 71

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 121802247 146 ---DVaiLVNNVGkshdiptpFAL------TSQEEMTDIITINCMGTLRATQLIVPGMMQRKRGLILTMGSFGGLLPTPL 216
Cdd:PRK06179  72 griDV--LVNNAG--------VGLagaaeeSSIAQAQALFDTNVFGILRMTRAVLPHMRAQGSGRIINISSVLGFLPAPY 141

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....
gi 121802247 217 LATYSGSKAFLQQWSTALGSELEEHGITVELVQ-AYLITSAMSKIRRASATIPD 269
Cdd:PRK06179 142 MALYAASKHAVEGYSESLDHEVRQFGIRVSLVEpAYTKTNFDANAPEPDSPLAE 195

classical (c) SDR, subgroup 2; Short-chain dehydrogenases/reductases (SDRs, aka Tyrosine-dependent oxidoreductases) 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 121802247  66 KGSWAVVTGASDGLGKEFSLQLARAGFNIVLVSRTASKLTTLSDEITSkyasvqTKTLAMDFARNED--SDYEKLKALVD 143
Cdd:cd05370    4 TGNTVLITGGTSGIGLALARKFLEAGNTVIITGRREERLAEAKKELPN------IHTIVLDVGDAESveALAEALLSEYP 77

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 121802247 144 ELDvaILVNNVG--KSHDIPTPfALTSQEEMTDIItINCMGTLRATQLIVPGMMQRKRGLILTMGSFGGLLPTPLLATYS 221
Cdd:cd05370   78 NLD--ILINNAGiqRPIDLRDP-ASDLDKADTEID-TNLIGPIRLIKAFLPHLKKQPEATIVNVSSGLAFVPMAANPVYC 153

                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 121802247 222 GSKAFLQQWSTALGSELEEHGITV-ELVQAYLITSAMSKIRRASATIPDPRS---FVKSVLSKIGRN 284
Cdd:cd05370  154 ATKAALHSYTLALRHQLKDTGVEVvEIVPPAVDTELHEERRNPDGGTPRKMPldeFVDEVVAGLERG 220