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 1443084662  58 GEWAVVTGPTSGIGRAMALELARHGLNLVLVGRDPAILREISGTVRSLHKVKTKTVVFDLSlvwtpDGDEPLRRLREAVE 137
Cdd:cd05356     1 GTWAVVTGATDGIGKAYAEELAKRGFNVILISRTQEKLDAVAKEIEEKYGVETKTIAADFS-----AGDDIYERIEKELE 75

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1443084662 138 GLDVGVVVNNAGVAKPGAVYLHEADVEAWVRMVRVNMSAVTEVTAVVLPGMVSRGRGAIVNIGSAGSEyIPTlPLYTMYA 217
Cdd:cd05356    76 GLDIGILVNNVGISHSIPEYFLETPEDELQDIINVNVMATLKMTRLILPGMVKRKKGAIVNISSFAGL-IPT-PLLATYS 153

                         170       180
                  ....*....|....*....|....*...
gi 1443084662 218 ATKRYVAQFSRSLHVEYASKGIHVQCQI 245
Cdd:cd05356   154 ASKAFLDFFSRALYEEYKSQGIDVQSLL 181

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1443084662  59 EWAVVTGPTSGIGRAMALELARHGLNLVLVGRDPAILREISGTVRSLhKVKTKTVVFDLSlvwtpDGDEPLRRLREAVE- 137
Cdd:pfam00106   1 KVALVTGASSGIGRAIAKRLAKEGAKVVLVDRSEEKLEAVAKELGAL-GGKALFIQGDVT-----DRAQVKALVEQAVEr 74

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1443084662 138 --GLDVGVVVNNAGVAKPgavyLHEADVEAWVRMVRVNMSAVTEVTAVVLPGMVSRGRGAIVNIGSAGSEYipTLPLYTM 215
Cdd:pfam00106  75 lgRLDILVNNAGITGLGP----FSELSDEDWERVIDVNLTGVFNLTRAVLPAMIKGSGGRIVNISSVAGLV--PYPGGSA 148

                         170       180
                  ....*....|....*....|....*...
gi 1443084662 216 YAATKRYVAQFSRSLHVEYASKGIHVQC 243
Cdd:pfam00106 149 YSASKAAVIGFTRSLALELAPHGIRVNA 176

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 1443084662  58 GEWAVVTGPTSGIGRAMALELARHGLNLVLVGRDPAILREISGTVRSLHKVKTKTVVFDLSlvwtpDGDEPLRRLREAVE 137
Cdd:cd05356     1 GTWAVVTGATDGIGKAYAEELAKRGFNVILISRTQEKLDAVAKEIEEKYGVETKTIAADFS-----AGDDIYERIEKELE 75

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1443084662 138 GLDVGVVVNNAGVAKPGAVYLHEADVEAWVRMVRVNMSAVTEVTAVVLPGMVSRGRGAIVNIGSAGSEyIPTlPLYTMYA 217
Cdd:cd05356    76 GLDIGILVNNVGISHSIPEYFLETPEDELQDIINVNVMATLKMTRLILPGMVKRKKGAIVNISSFAGL-IPT-PLLATYS 153

                         170       180
                  ....*....|....*....|....*...
gi 1443084662 218 ATKRYVAQFSRSLHVEYASKGIHVQCQI 245
Cdd:cd05356   154 ASKAFLDFFSRALYEEYKSQGIDVQSLL 181

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 1443084662  61 AVVTGPTSGIGRAMALELARHGLNLVLVGRDPAILREisgtVRSLHKVKTKTVVFDLSlvwtpDGDEpLRRLREAVE--- 137
Cdd:COG4221     8 ALITGASSGIGAATARALAAAGARVVLAARRAERLEA----LAAELGGRALAVPLDVT-----DEAA-VEAAVAAAVaef 77

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1443084662 138 -GLDvgvvvnnagvakpGAVY---------LHEADVEAWVRMVRVNMSAVTEVTAVVLPGMVSRGRGAIVNIGSAGSEYi 207
Cdd:COG4221    78 gRLD-------------VLVNnagvallgpLEELDPEDWDRMIDVNVKGVLYVTRAALPAMRARGSGHIVNISSIAGLR- 143

                         170       180       190
                  ....*....|....*....|....*....|....
gi 1443084662 208 pTLPLYTMYAATKRYVAQFSRSLHVEYASKGIHV 241
Cdd:COG4221   144 -PYPGGAVYAATKAAVRGLSESLRAELRPTGIRV 176

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 1443084662  58 GEWAVVTGPTSGIGRAMALELARHGLNLVLVGRDPAILREISGTVRSLHkVKTKTVVFDLSlvwtpDGDEPLRRLREAVE 137
Cdd:COG1028     6 GKVALVTGGSSGIGRAIARALAAEGARVVITDRDAEALEAAAAELRAAG-GRALAVAADVT-----DEAAVEALVAAAVA 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1443084662 138 ---GLDVGVVVNNAGVAKPgavyLHEADVEAWVRMVRVNMSAVTEVTAVVLPGMVSRGRGAIVNIGSAGSeYIPTlPLYT 214
Cdd:COG1028    80 afgRLDILVNNAGITPPGP----LEELTEEDWDRVLDVNLKGPFLLTRAALPHMRERGGGRIVNISSIAG-LRGS-PGQA 153

                         170       180
                  ....*....|....*....|....*..
gi 1443084662 215 MYAATKRYVAQFSRSLHVEYASKGIHV 241
Cdd:COG1028   154 AYAASKAAVVGLTRSLALELAPRGIRV 180

classical (c) SDR, subgroup 5; These proteins are members of the classical SDR family, with a canonical active site tetrad and a typical Gly-rich NAD-binding motif. SDRs are a functionally diverse family of oxidoreductases that have a single domain with a structurally conserved Rossmann fold (alpha/beta folding pattern with a central beta-sheet), an NAD(P)(H)-binding region, and a structurally diverse C-terminal region. Classical SDRs are typically about 250 residues long, while extended SDRs are approximately 350 residues. Sequence identity between different SDR enzymes are typically in the 15-30% range, but the enzymes share the Rossmann fold NAD-binding motif and characteristic NAD-binding and catalytic sequence patterns. These enzymes catalyze a wide range of activities including the metabolism of steroids, cofactors, carbohydrates, lipids, aromatic compounds, and amino acids, and act in redox sensing. Classical SDRs have an TGXXX[AG]XG cofactor binding motif and a YXXXK active site motif, with the Tyr residue of the active site motif serving as a critical catalytic residue (Tyr-151, human 15-hydroxyprostaglandin dehydrogenase (15-PGDH) numbering). In addition to the Tyr and Lys, there is often an upstream Ser (Ser-138, 15-PGDH numbering) and/or an Asn (Asn-107, 15-PGDH numbering) contributing to the active site; while substrate binding is in the C-terminal region, which determines specificity. The standard reaction mechanism is a 4-pro-S hydride transfer and proton relay involving the conserved Tyr and Lys, a water molecule stabilized by Asn, and nicotinamide. Extended SDRs have additional elements in the C-terminal region, and typically have a TGXXGXXG cofactor binding motif. Complex (multidomain) SDRs such as ketoreductase domains of fatty acid synthase have a GGXGXXG NAD(P)-binding motif and an altered active site motif (YXXXN). Fungal type ketoacyl reductases have a TGXXXGX(1-2)G NAD(P)-binding motif. Some atypical SDRs have lost catalytic activity and/or have an unusual NAD(P)-binding motif and missing or unusual active site residues. Reactions catalyzed within the SDR family include isomerization, decarboxylation, epimerization, C=N bond reduction, dehydratase activity, dehalogenation, Enoyl-CoA reduction, and carbonyl-alcohol oxidoreduction.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1443084662  61 AVVTGPTSGIGRAMALELARHGLNLVLVGRDPAILREISGTVRSLHKVKTKTVVFDLSlvwtpdgDEPLrrLREAVEGLD 140
Cdd:cd05346     3 VLITGASSGIGEATARRFAKAGAKLILTGRRAERLQELADELGAKFPVKVLPLQLDVS-------DRES--IEAALENLP 73

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1443084662 141 VGVVVNNAGVAKPGAVY----LHEADVEAWVRMVRVNMSAVTEVTAVVLPGMVSRGRGAIVNIGS-AGSEYIPTlplYTM 215
Cdd:cd05346    74 EEFRDIDILVNNAGLALgldpAQEADLEDWETMIDTNVKGLLNVTRLILPIMIARNQGHIINLGSiAGRYPYAG---GNV 150

                         170       180
                  ....*....|....*....|....*.
gi 1443084662 216 YAATKRYVAQFSRSLHVEYASKGIHV 241
Cdd:cd05346   151 YCATKAAVRQFSLNLRKDLIGTGIRV 176

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1443084662  61 AVVTGPTSGIGRAMALELARHGLNLVLVGR-DPAILREISGTVRSLHkVKTKTVVFDLSlvwtpDGDEPLRRLREAVEGL 139
Cdd:PRK12825    9 ALVTGAARGLGRAIALRLARAGADVVVHYRsDEEAAEELVEAVEALG-RRAQAVQADVT-----DKAALEAAVAAAVERF 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1443084662 140 dvgvvvnnagvakpGAVY-------------LHEADVEAWVRMVRVNMSAVTEVTAVVLPGMVSRGRGAIVNIGSAGSey 206
Cdd:PRK12825   83 --------------GRIDilvnnagifedkpLADMSDDEWDEVIDVNLSGVFHLLRAVVPPMRKQRGGRIVNISSVAG-- 146

                         170       180       190
                  ....*....|....*....|....*....|....*..
gi 1443084662 207 IPTLPLYTMYAATKRYVAQFSRSLHVEYASKGIHVQC 243
Cdd:PRK12825  147 LPGWPGRSNYAAAKAGLVGLTKALARELAEYGITVNM 183

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1443084662  58 GEWAVVTGPTSGIGRAMALELARHGLNLVLVGRDPAILREISGTVRSLhKVKTKTVVFDLSlvwtpDGDE---PLRRLRE 134
Cdd:PRK07666    7 GKNALITGAGRGIGRAVAIALAKEGVNVGLLARTEENLKAVAEEVEAY-GVKVVIATADVS-----DYEEvtaAIEQLKN 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1443084662 135 AVEGLDVGVVVNNAGvaKPGAVYlhEADVEAWVRMVRVNMSAVTEVTAVVLPGMVSRGRGAIVNIGS-AGSEYIPTLply 213
Cdd:PRK07666   81 ELGSIDILINNAGIS--KFGKFL--ELDPAEWEKIIQVNLMGVYYATRAVLPSMIERQSGDIINISStAGQKGAAVT--- 153

                         170       180
                  ....*....|....*....|....*...
gi 1443084662 214 TMYAATKRYVAQFSRSLHVEYASKGIHV 241
Cdd:PRK07666  154 SAYSASKFGVLGLTESLMQEVRKHNIRV 181

SDR family oxidoreductase;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1443084662  61 AVVTGPTSGIGRAMALELARHGLNLVLVGRDPAILREISGTVRSlhkvkTKTVVF---DLSlvwtpDGDEPLRRLREAVE 137
Cdd:PRK07231    8 AIVTGASSGIGEGIARRFAAEGARVVVTDRNEEAAERVAAEILA-----GGRAIAvaaDVS-----DEADVEAAVAAALE 77

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1443084662 138 ---GLDVGVV-VNNAGVAKPgavyLHEADVEAWVRMVRVNMSAVTEVTAVVLPGMVSRGRGAIVNIGSAGSeyIPTLPLY 213
Cdd:PRK07231   78 rfgSVDILVNnAGTTHRNGP----LLDVDEAEFDRIFAVNVKSPYLWTQAAVPAMRGEGGGAIVNVASTAG--LRPRPGL 151

                         170       180       190
                  ....*....|....*....|....*....|
gi 1443084662 214 TMYAATKRYVAQFSRSLHVEYASKGIHVQC 243
Cdd:PRK07231  152 GWYNASKGAVITLTKALAAELGPDKIRVNA 181

classical (c) SDR, subgroup 11; SDRs are a functionally diverse family of oxidoreductases that have a single domain with a structurally conserved Rossmann fold (alpha/beta folding pattern with a central beta-sheet), an NAD(P)(H)-binding region, and a structurally diverse C-terminal region. Classical SDRs are typically about 250 residues long, while extended SDRs are approximately 350 residues. Sequence identity between different SDR enzymes are typically in the 15-30% range, but the enzymes share the Rossmann fold NAD-binding motif and characteristic NAD-binding and catalytic sequence patterns. These enzymes catalyze a wide range of activities including the metabolism of steroids, cofactors, carbohydrates, lipids, aromatic compounds, and amino acids, and act in redox sensing. Classical SDRs have an TGXXX[AG]XG cofactor binding motif and a YXXXK active site motif, with the Tyr residue of the active site motif serving as a critical catalytic residue (Tyr-151, human 15-hydroxyprostaglandin dehydrogenase (15-PGDH) numbering). In addition to the Tyr and Lys, there is often an upstream Ser (Ser-138, 15-PGDH numbering) and/or an Asn (Asn-107, 15-PGDH numbering) contributing to the active site; while substrate binding is in the C-terminal region, which determines specificity. The standard reaction mechanism is a 4-pro-S hydride transfer and proton relay involving the conserved Tyr and Lys, a water molecule stabilized by Asn, and nicotinamide. Extended SDRs have additional elements in the C-terminal region, and typically have a TGXXGXXG cofactor binding motif. Complex (multidomain) SDRs such as ketoreductase domains of fatty acid synthase have a GGXGXXG NAD(P)-binding motif and an altered active site motif (YXXXN). Fungal type ketoacyl reductases have a TGXXXGX(1-2)G NAD(P)-binding motif. Some atypical SDRs have lost catalytic activity and/or have an unusual NAD(P)-binding motif and missing or unusual active site residues. Reactions catalyzed within the SDR family include isomerization, decarboxylation, epimerization, C=N bond reduction, dehydratase activity, dehalogenation, Enoyl-CoA reduction, and carbonyl-alcohol oxidoreduction.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1443084662  61 AVVTGPTSGIGRAMALELARHGLNLVLVGRDPAILREISGTV--RSLHKVKTKTVVFDLSlvwtpdGDEPLRR-LREAVE 137
Cdd:cd05364     6 AIITGSSSGIGAGTAILFARLGARLALTGRDAERLEETRQSClqAGVSEKKILLVVADLT------EEEGQDRiISTTLA 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1443084662 138 G---LDVGVVVNNAGVakPGAVylHEADVEAWVRMVRVNMSAVTEVTAVVLPGMVSrGRGAIVNIGSAGSeyIPTLPLYT 214
Cdd:cd05364    80 KfgrLDILVNNAGILA--KGGG--EDQDIEEYDKVMNLNLRAVIYLTKLAVPHLIK-TKGEIVNVSSVAG--GRSFPGVL 152

                         170       180
                  ....*....|....*....|....*..
gi 1443084662 215 MYAATKRYVAQFSRSLHVEYASKGIHV 241
Cdd:cd05364   153 YYCISKAALDQFTRCTALELAPKGVRV 179

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 1443084662  61 AVVTGPTSGIGRAMALELARHGLNLVLVGRDPAilREISGTVRSLHKVKTKTVVFDLSLVWTPDGDEPLRRLREAVEGLD 140
Cdd:cd05359     1 ALVTGGSRGIGKAIALRLAERGADVVINYRKSK--DAAAEVAAEIEELGGKAVVVRADVSQPQDVEEMFAAVKERFGRLD 78

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1443084662 141 VGVVVNNAGVAKPgavyLHEADVEAWVRMVRVNMSAVTEVTAVVLPGMVSRGRGAIVNIGSAGSEYipTLPLYTMYAATK 220
Cdd:cd05359    79 VLVSNAAAGAFRP----LSELTPAHWDAKMNTNLKALVHCAQQAAKLMRERGGGRIVAISSLGSIR--ALPNYLAVGTAK 152

                         170       180
                  ....*....|....*....|...
gi 1443084662 221 RYVAQFSRSLHVEYASKGIHVQC 243
Cdd:cd05359   153 AALEALVRYLAVELGPRGIRVNA 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 1443084662  58 GEWAVVTGPTSGIGRAMALELARHGLNLVLVGRDPAILREISGTVRSLhKVKTKTVVFDLSlvwtpDGDEPLRrlreAVE 137
Cdd:cd05347     5 GKVALVTGASRGIGFGIASGLAEAGANIVINSRNEEKAEEAQQLIEKE-GVEATAFTCDVS-----DEEAIKA----AVE 74

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1443084662 138 GLDVGVVVNNAGVAKPGAVYLHEAD---VEAWVRMVRVNMSAVTEVTAVVLPGMVSRGRGAIVNIGSAGSEYipTLPLYT 214
Cdd:cd05347    75 AIEEDFGKIDILVNNAGIIRRHPAEefpEAEWRDVIDVNLNGVFFVSQAVARHMIKQGHGKIINICSLLSEL--GGPPVP 152

                         170       180
                  ....*....|....*....|....*..
gi 1443084662 215 MYAATKRYVAQFSRSLHVEYASKGIHV 241
Cdd:cd05347   153 AYAASKGGVAGLTKALATEWARHGIQV 179

d-3-hydroxybutyrate dehydrogenase (HBDH), classical (c) SDRs; DHBDH, an NAD+ -dependent enzyme, catalyzes the interconversion of D-3-hydroxybutyrate and acetoacetate. It is a classical SDR, with the canonical NAD-binding motif and active site tetrad. 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 1443084662  58 GEWAVVTGPTSGIGRAMALELARHGLNLVLVG-RDPAILREISGTVRSLHKVKTKTVVFDLSLVwtPDGDEPLRRLREAV 136
Cdd:cd08940     2 GKVALVTGSTSGIGLGIARALAAAGANIVLNGfGDAAEIEAVRAGLAAKHGVKVLYHGADLSKP--AAIEDMVAYAQRQF 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1443084662 137 EGLDVGVVVNNAGVAKPgavyLHEADVEAWVRMVRVNMSAVTEVTAVVLPGMVSRGRGAIVNIGSA----GSeyiptlPL 212
Cdd:cd08940    80 GGVDILVNNAGIQHVAP----IEDFPTEKWDAIIALNLSAVFHTTRLALPHMKKQGWGRIINIASVhglvAS------AN 149

                         170       180
                  ....*....|....*....|....*....
gi 1443084662 213 YTMYAATKRYVAQFSRSLHVEYASKGIHV 241
Cdd:cd08940   150 KSAYVAAKHGVVGLTKVVALETAGTGVTC 178

human DHRS6-like, classical (c) SDRs; Human DHRS6, and similar proteins. These proteins are classical SDRs, with a canonical active site tetrad and a close match to the typical Gly-rich NAD-binding motif. Human DHRS6 is a cytosolic type 2 (R)-hydroxybutyrate dehydrogenase, which catalyses the conversion of (R)-hydroxybutyrate to acetoacetate. Also included in this subgroup is Escherichia coli UcpA (upstream cys P). 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. Note: removed : needed to make this chiodl smaller when drew final trees: rmeoved text form description: Other proteins in this subgroup include Thermoplasma acidophilum aldohexose dehydrogenase, which has high dehydrogenase activity against D-mannose, Bacillus subtilis BacC involved in the biosynthesis of the dipeptide bacilysin and its antibiotic moiety anticapsin, Sphingomonas paucimobilis strain B90 LinC, involved in the degradation of hexachlorocyclohexane isomers...... P).

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1443084662  58 GEWAVVTGPTSGIGRAMALELARHGLNLVLVGRDPAILREISGTVRslhkvkTKTVVFDLslvwtpdgdeplrRLREAVE 137
Cdd:cd05368     2 GKVALITAAAQGIGRAIALAFAREGANVIATDINEEKLKELERGPG------ITTRVLDV-------------TDKEQVA 62

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1443084662 138 GLDVGVVVNNAGVAKPGAVY---LHEADVEAWVRMVRVNMSAVTEVTAVVLPGMVSRGRGAIVNIGSAGSEyIPTLPLYT 214
Cdd:cd05368    63 ALAKEEGRIDVLFNCAGFVHhgsILDCEDDDWDFAMNLNVRSMYLMIKAVLPKMLARKDGSIINMSSVASS-IKGVPNRF 141

                         170       180
                  ....*....|....*....|....*....
gi 1443084662 215 MYAATKRYVAQFSRSLHVEYASKGIHVQC 243
Cdd:cd05368   142 VYSTTKAAVIGLTKSVAADFAQQGIRCNA 170

classical (c) SDR, subgroup 6; These proteins are members of the classical SDR family, with a canonical active site tetrad and a fairly well conserved typical Gly-rich NAD-binding motif. SDRs are a functionally diverse family of oxidoreductases that have a single domain with a structurally conserved Rossmann fold (alpha/beta folding pattern with a central beta-sheet), an NAD(P)(H)-binding region, and a structurally diverse C-terminal region. Classical SDRs are typically about 250 residues long, while extended SDRS are approximately 350 residues. Sequence identity between different SDR enzymes are typically in the 15-30% range, but the enzymes share the Rossmann fold NAD-binding motif and characteristic NAD-binding and catalytic sequence patterns. These enzymes have a 3-glycine N-terminal NAD(P)(H)-binding pattern (typically, TGxxxGxG in classical SDRs and TGxxGxxG in extended SDRs), while substrate binding is in the C-terminal region. A critical catalytic Tyr residue (Tyr-151, human 15-hydroxyprostaglandin dehydrogenase (15-PGDH) numbering), is often found in a conserved YXXXK pattern. In addition to the Tyr and Lys, there is often an upstream Ser (Ser-138, 15-PGDH numbering) and/or an Asn (Asn-107, 15-PGDH numbering) or additional Ser, contributing to the active site. Substrates for these enzymes include sugars, steroids, alcohols, and aromatic compounds. The standard reaction mechanism is a proton relay involving the conserved Tyr and Lys, as well as Asn (or Ser). Some SDR family members, including 17 beta-hydroxysteroid dehydrogenase contain an additional helix-turn-helix motif that is not generally found among SDRs.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1443084662  61 AVVTGPTSGIGRAMALELARHGLNLVLVGRDPAILREISGTVRSLHKVKTKtVVFDLSlvwtpdgDEPL-----RRLREA 135
Cdd:cd05350     1 VLITGASSGIGRALAREFAKAGYNVALAARRTDRLDELKAELLNPNPSVEV-EILDVT-------DEERnqlviAELEAE 72

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1443084662 136 VEGLDVGVVVNNAGVAKPGAvylhEADVEAWVRMVRVNMSAVTEVTAVVLPGMVSRGRGAIVNIGS-AGSEYIPTLPlyt 214
Cdd:cd05350    73 LGGLDLVIINAGVGKGTSLG----DLSFKAFRETIDTNLLGAAAILEAALPQFRAKGRGHLVLISSvAALRGLPGAA--- 145

                         170       180
                  ....*....|....*....|....*....
gi 1443084662 215 MYAATKRYVAQFSRSLHVEYASKGIHVQC 243
Cdd:cd05350   146 AYSASKAALSSLAESLRYDVKKRGIRVTV 174

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 1443084662  58 GEWAVVTGPTSGIGRAMALELARHGLNLVLVGRDPAILREISGTVRSLHkvktkTVVFDLSLVwtpdgdEPLRRLREAVE 137
Cdd:cd05370     5 GNTVLITGGTSGIGLALARKFLEAGNTVIITGRREERLAEAKKELPNIH-----TIVLDVGDA------ESVEALAEALL 73

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1443084662 138 G----LDvgvvvnnAGVAKPGAVYLHE-----ADVEAWVRMVRVNMSAVTEVTAVVLPGMVSRGRGAIVNIGSaGSEYIP 208
Cdd:cd05370    74 SeypnLD-------ILINNAGIQRPIDlrdpaSDLDKADTEIDTNLIGPIRLIKAFLPHLKKQPEATIVNVSS-GLAFVP 145

                         170       180       190
                  ....*....|....*....|....*....|...
gi 1443084662 209 tLPLYTMYAATKRYVAQFSRSLHVEYASKGIHV 241
Cdd:cd05370   146 -MAANPVYCATKAALHSYTLALRHQLKDTGVEV 177