Rossmann-fold NAD(P)(+)-binding proteins; A large family of proteins that share a Rossmann-fold NAD(P)H/NAD(P)(+) binding (NADB) domain. The NADB domain is found in numerous dehydrogenases of metabolic pathways such as glycolysis, and many other redox enzymes. NAD binding involves numerous hydrogen-bonds and van der Waals contacts, in particular H-bonding of residues in a turn between the first strand and the subsequent helix of the Rossmann-fold topology. Characteristically, this turn exhibits a consensus binding pattern similar to GXGXXG, in which the first 2 glycines participate in NAD(P)-binding, and the third facilitates close packing of the helix to the beta-strand. Typically, proteins in this family contain a second domain in addition to the NADB domain, which is responsible for specifically binding a substrate and catalyzing a particular enzymatic reaction.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720379773  24 GLTRRNPLSNKVALVTASTDGIGFAIARRLAEDGAHVVVSSRKQQNVDRAVATLQGEGLSVTGIVCHVGKAEDREKLITT 103
Cdd:cd08936     1 GVTRRDPLANKVALVTASTDGIGLAIARRLAQDGAHVVVSSRKQQNVDRAVATLQGEGLSVTGTVCHVGKAEDRERLVAT 80

                          90       100       110
                  ....*....|....*....|....*....|....
gi 1720379773 104 ALKRHQGIDILVSNAAVNPFFGNLMDVTEEVWDK 137
Cdd:cd08936    81 AVNLHGGVDILVSNAAVNPFFGNILDSTEEVWDK 114

Porcine peroxisomal carbonyl reductase like, classical (c) SDR; This subgroup contains porcine peroxisomal carbonyl reductase and similar proteins. The porcine enzyme efficiently reduces retinals. This subgroup also includes human dehydrogenase/reductase (SDR family) member 4 (DHRS4), and human DHRS4L1. DHRS4 is a peroxisomal enzyme with 3beta-hydroxysteroid dehydrogenase activity; it catalyzes the reduction of 3-keto-C19/C21-steroids into 3beta-hydroxysteroids more efficiently than it does the retinal reduction. The human DHRS4 gene cluster contains DHRS4, DHRS4L2 and DHRS4L1. DHRS4L2 and DHRS4L1 are paralogs of DHRS4, DHRS4L2 being the most recent member. SDRs are a functionally diverse family of oxidoreductases that have a single domain with a structurally conserved Rossmann fold (alpha/beta folding pattern with a central beta-sheet), an NAD(P)(H)-binding region, and a structurally diverse C-terminal region. Classical SDRs are typically about 250 residues long, while extended SDRs are approximately 350 residues. Sequence identity between different SDR enzymes are typically in the 15-30% range, but the enzymes share the Rossmann fold NAD-binding motif and characteristic NAD-binding and catalytic sequence patterns. These enzymes catalyze a wide range of activities including the metabolism of steroids, cofactors, carbohydrates, lipids, aromatic compounds, and amino acids, and act in redox sensing. Classical SDRs have an TGXXX[AG]XG cofactor binding motif and a YXXXK active site motif, with the Tyr residue of the active site motif serving as a critical catalytic residue (Tyr-151, human 15-hydroxyprostaglandin dehydrogenase (15-PGDH) numbering). In addition to the Tyr and Lys, there is often an upstream Ser (Ser-138, 15-PGDH numbering) and/or an Asn (Asn-107, 15-PGDH numbering) contributing to the active site; while substrate binding is in the C-terminal region, which determines specificity. The standard reaction mechanism is a 4-pro-S hydride transfer and proton relay involving the conserved Tyr and Lys, a water molecule stabilized by Asn, and nicotinamide. Extended SDRs have additional elements in the C-terminal region, and typically have a TGXXGXXG cofactor binding motif. Complex (multidomain) SDRs such as ketoreductase domains of fatty acid synthase have a GGXGXXG NAD(P)-binding motif and an altered active site motif (YXXXN). Fungal type ketoacyl reductases have a TGXXXGX(1-2)G NAD(P)-binding motif. Some atypical SDRs have lost catalytic activity and/or have an unusual NAD(P)-binding motif and missing or unusual active site residues. Reactions catalyzed within the SDR family include isomerization, decarboxylation, epimerization, C=N bond reduction, dehydratase activity, dehalogenation, Enoyl-CoA reduction, and carbonyl-alcohol oxidoreduction.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720379773  24 GLTRRNPLSNKVALVTASTDGIGFAIARRLAEDGAHVVVSSRKQQNVDRAVATLQGEGLSVTGIVCHVGKAEDREKLITT 103
Cdd:cd08936     1 GVTRRDPLANKVALVTASTDGIGLAIARRLAQDGAHVVVSSRKQQNVDRAVATLQGEGLSVTGTVCHVGKAEDRERLVAT 80

                          90       100       110
                  ....*....|....*....|....*....|....
gi 1720379773 104 ALKRHQGIDILVSNAAVNPFFGNLMDVTEEVWDK 137
Cdd:cd08936    81 AVNLHGGVDILVSNAAVNPFFGNILDSTEEVWDK 114

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 1720379773  29 NPLSNKVALVTASTDGIGFAIARRLAEDGAHVVVSSRKQQNVDRAVATLQGEGLSVTGIVCHVGKAEDREKLITTALKRH 108
Cdd:COG1028     2 TRLKGKVALVTGGSSGIGRAIARALAAEGARVVITDRDAEALEAAAAELRAAGGRALAVAADVTDEAAVEALVAAAVAAF 81

                          90       100
                  ....*....|....*....|....*....
gi 1720379773 109 QGIDILVSNAAVNPfFGNLMDVTEEVWDK 137
Cdd:COG1028    82 GRLDILVNNAGITP-PGPLEELTEEDWDR 109

This enzymatic domain is part of bacterial polyketide synthases; It catalyses the first step in the reductive modification of the beta-carbonyl centres in the growing polyketide chain. It uses NADPH to reduce the keto group to a hydroxy group.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720379773   34 KVALVTASTDGIGFAIARRLAEDGA-HVVVSSR---KQQNVDRAVATLQGEGLSVTGIVCHVGKAEDREKLITTALKRHQ 109
Cdd:smart00822   1 GTYLITGGLGGLGRALARWLAERGArRLVLLSRsgpDAPGAAALLAELEAAGARVTVVACDVADRDALAAVLAAIPAVEG 80

                           90       100
                   ....*....|....*....|....*..
gi 1720379773  110 GIDILVsNAAVNPFFGNLMDVTEEVWD 136
Cdd:smart00822  81 PLTGVI-HAAGVLDDGVLASLTPERFA 106

Porcine peroxisomal carbonyl reductase like, classical (c) SDR; This subgroup contains porcine peroxisomal carbonyl reductase and similar proteins. The porcine enzyme efficiently reduces retinals. This subgroup also includes human dehydrogenase/reductase (SDR family) member 4 (DHRS4), and human DHRS4L1. DHRS4 is a peroxisomal enzyme with 3beta-hydroxysteroid dehydrogenase activity; it catalyzes the reduction of 3-keto-C19/C21-steroids into 3beta-hydroxysteroids more efficiently than it does the retinal reduction. The human DHRS4 gene cluster contains DHRS4, DHRS4L2 and DHRS4L1. DHRS4L2 and DHRS4L1 are paralogs of DHRS4, DHRS4L2 being the most recent member. SDRs are a functionally diverse family of oxidoreductases that have a single domain with a structurally conserved Rossmann fold (alpha/beta folding pattern with a central beta-sheet), an NAD(P)(H)-binding region, and a structurally diverse C-terminal region. Classical SDRs are typically about 250 residues long, while extended SDRs are approximately 350 residues. Sequence identity between different SDR enzymes are typically in the 15-30% range, but the enzymes share the Rossmann fold NAD-binding motif and characteristic NAD-binding and catalytic sequence patterns. These enzymes catalyze a wide range of activities including the metabolism of steroids, cofactors, carbohydrates, lipids, aromatic compounds, and amino acids, and act in redox sensing. Classical SDRs have an TGXXX[AG]XG cofactor binding motif and a YXXXK active site motif, with the Tyr residue of the active site motif serving as a critical catalytic residue (Tyr-151, human 15-hydroxyprostaglandin dehydrogenase (15-PGDH) numbering). In addition to the Tyr and Lys, there is often an upstream Ser (Ser-138, 15-PGDH numbering) and/or an Asn (Asn-107, 15-PGDH numbering) contributing to the active site; while substrate binding is in the C-terminal region, which determines specificity. The standard reaction mechanism is a 4-pro-S hydride transfer and proton relay involving the conserved Tyr and Lys, a water molecule stabilized by Asn, and nicotinamide. Extended SDRs have additional elements in the C-terminal region, and typically have a TGXXGXXG cofactor binding motif. Complex (multidomain) SDRs such as ketoreductase domains of fatty acid synthase have a GGXGXXG NAD(P)-binding motif and an altered active site motif (YXXXN). Fungal type ketoacyl reductases have a TGXXXGX(1-2)G NAD(P)-binding motif. Some atypical SDRs have lost catalytic activity and/or have an unusual NAD(P)-binding motif and missing or unusual active site residues. Reactions catalyzed within the SDR family include isomerization, decarboxylation, epimerization, C=N bond reduction, dehydratase activity, dehalogenation, Enoyl-CoA reduction, and carbonyl-alcohol oxidoreduction.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720379773  24 GLTRRNPLSNKVALVTASTDGIGFAIARRLAEDGAHVVVSSRKQQNVDRAVATLQGEGLSVTGIVCHVGKAEDREKLITT 103
Cdd:cd08936     1 GVTRRDPLANKVALVTASTDGIGLAIARRLAQDGAHVVVSSRKQQNVDRAVATLQGEGLSVTGTVCHVGKAEDRERLVAT 80

                          90       100       110
                  ....*....|....*....|....*....|....
gi 1720379773 104 ALKRHQGIDILVSNAAVNPFFGNLMDVTEEVWDK 137
Cdd:cd08936    81 AVNLHGGVDILVSNAAVNPFFGNILDSTEEVWDK 114

SDR family oxidoreductase;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720379773  31 LSNKVALVTASTDGIGFAIARRLAEDGAHVVVSSRKQQNVDRAVATLQGEGLSVTGIVCHVGKAEDREKLITTALKRHQG 110
Cdd:PRK07035    6 LTGKIALVTGASRGIGEAIAKLLAQQGAHVIVSSRKLDGCQAVADAIVAAGGKAEALACHIGEMEQIDALFAHIRERHGR 85

                          90       100
                  ....*....|....*....|....*..
gi 1720379773 111 IDILVSNAAVNPFFGNLMDVTEEVWDK 137
Cdd:PRK07035   86 LDILVNNAAANPYFGHILDTDLGAFQK 112

3-oxoacyl-ACP reductase FabG;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720379773  31 LSNKVALVTASTDGIGFAIARRLAEDGAHVVVSSRKQQNVDRAVATLQGEGLSVTGIVCHVGKAEDREKLITTALKRHQG 110
Cdd:PRK05653    3 LQGKTALVTGASRGIGRAIALRLAADGAKVVIYDSNEEAAEALAAELRAAGGEARVLVFDVSDEAAVRALIEAAVEAFGA 82

                          90       100
                  ....*....|....*....|....*..
gi 1720379773 111 IDILVSNAAVNPfFGNLMDVTEEVWDK 137
Cdd:PRK05653   83 LDILVNNAGITR-DALLPRMSEEDWDR 108

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720379773  34 KVALVTASTDGIGFAIARRLAEDGAHVVVSSRKQQNVDRAVATLQGEGLSVTGIVCHVGKAEDREKLITTALKRHQGIDI 113
Cdd:pfam00106   1 KVALVTGASSGIGRAIAKRLAKEGAKVVLVDRSEEKLEAVAKELGALGGKALFIQGDVTDRAQVKALVEQAVERLGRLDI 80

                          90       100
                  ....*....|....*....|....
gi 1720379773 114 LVSNAAVNPfFGNLMDVTEEVWDK 137
Cdd:pfam00106  81 LVNNAGITG-LGPFSELSDEDWER 103

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720379773  30 PLSNKVALVTASTDGIGFAIARRLAEDGAHVVVSSRK-QQNVDRAVATLQGEGLSVTGIVCHVGKAEDREKLITTALKRH 108
Cdd:PRK12825    3 SLMGRVALVTGAARGLGRAIALRLARAGADVVVHYRSdEEAAEELVEAVEALGRRAQAVQADVTDKAALEAAVAAAVERF 82

                          90       100
                  ....*....|....*....|....*...
gi 1720379773 109 QGIDILVSNAAVNPfFGNLMDVTEEVWD 136
Cdd:PRK12825   83 GRIDILVNNAGIFE-DKPLADMSDDEWD 109

Short-chain dehydrogenase [General function prediction only];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720379773  31 LSNKVALVTASTDGIGFAIARRLAEDGAHVVVSSRKQQNVDRAVATLQGEGLSVTGIVCHVGKAEDREKLITTALKRHQG 110
Cdd:COG0300     3 LTGKTVLITGASSGIGRALARALAARGARVVLVARDAERLEALAAELRAAGARVEVVALDVTDPDAVAALAEAVLARFGP 82

                          90       100
                  ....*....|....*....|....*..
gi 1720379773 111 IDILVSNAAVNPfFGNLMDVTEEVWDK 137
Cdd:COG0300    83 IDVLVNNAGVGG-GGPFEELDLEDLRR 108

3-hydroxybutyrate dehydrogenase; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720379773  31 LSNKVALVTASTDGIGFAIARRLAEDGAHVVVSSRKQQNVDRAVATLQGEGLSVTGIVCHVGKAEDREKLITTALKRHQG 110
Cdd:PRK12429    2 LKGKVALVTGAASGIGLEIALALAKEGAKVVIADLNDEAAAAAAEALQKAGGKAIGVAMDVTDEEAINAGIDYAVETFGG 81

                          90       100       110
                  ....*....|....*....|....*....|
gi 1720379773 111 IDILVSNAA---VNPffgnLMDVTEEVWDK 137
Cdd:PRK12429   82 VDILVNNAGiqhVAP----IEDFPTEKWKK 107

SDR family oxidoreductase;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720379773  31 LSNKVALVTASTDGIGFAIARRLAEDGAHVVVSSRKQQNVDRAVATLQGEGlSVTGIVCHVGKAEDREKLITTALKRHQG 110
Cdd:PRK07326    4 LKGKVALITGGSKGIGFAIAEALLAEGYKVAITARDQKELEEAAAELNNKG-NVLGLAADVRDEADVQRAVDAIVAAFGG 82

                          90       100
                  ....*....|....*....|....*.
gi 1720379773 111 IDILVSNAAVNpFFGNLMDVTEEVWD 136
Cdd:PRK07326   83 LDVLIANAGVG-HFAPVEELTPEEWR 107

short chain dehydrogenase; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720379773  27 RRNPLSNKVALVTASTDGIGFAIARRLAEDGAHVVVSSRKQQNVDRAVATLqgEGLSVTGIVCHVGKAEDREKLITTALK 106
Cdd:PRK12829    5 LLKPLDGLRVLVTGGASGIGRAIAEAFAEAGARVHVCDVSEAALAATAARL--PGAKVTATVADVADPAQVERVFDTAVE 82

                          90       100       110
                  ....*....|....*....|....*....|
gi 1720379773 107 RHQGIDILVSNAAVNPFFGNLMDVTEEVWD 136
Cdd:PRK12829   83 RFGGLDVLVNNAGIAGPTGGIDEITPEQWE 112

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 1720379773  34 KVALVTASTDGIGFAIARRLAEDGAHVVVSSRKQQNVDRAVATLQGEGLSVTGIVCHVGKAEDREKLITTALKRHQGIDI 113
Cdd:cd05333     1 KVALVTGASRGIGRAIALRLAAEGAKVAVTDRSEEAAAETVEEIKALGGNAAALEADVSDREAVEALVEKVEAEFGPVDI 80

                          90       100
                  ....*....|....*....|....*.
gi 1720379773 114 LVSNAAV--NPFFgnlMDVTEEVWDK 137
Cdd:cd05333    81 LVNNAGItrDNLL---MRMSEEDWDA 103

bifunctional aldolase/short-chain dehydrogenase;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720379773  30 PLSNKVALVTASTDGIGFAIARRLAEDGAHVVVSSRKQQNVDRAVATLQGEGlSVTGIVCHVGKAEDREKLITTALKRHQ 109
Cdd:PRK08324  419 PLAGKVALVTGAAGGIGKATAKRLAAEGACVVLADLDEEAAEAAAAELGGPD-RALGVACDVTDEAAVQAAFEEAALAFG 497

                          90       100
                  ....*....|....*....|....*...
gi 1720379773 110 GIDILVSNAAVNPfFGNLMDVTEEVWDK 137
Cdd:PRK08324  498 GVDIVVSNAGIAI-SGPIEETSDEDWRR 524

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 1720379773  31 LSNKVALVTASTDGIGFAIARRLAEDGAHVVVSSRKQQNVDRAVAtlqgEGLSVTGIVCHVGKAEDREKLITTALKRHQG 110
Cdd:cd05370     3 LTGNTVLITGGTSGIGLALARKFLEAGNTVIITGRREERLAEAKK----ELPNIHTIVLDVGDAESVEALAEALLSEYPN 78

                          90
                  ....*....|
gi 1720379773 111 IDILVSNAAV 120
Cdd:cd05370    79 LDILINNAGI 88

short chain dehydrogenase; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720379773  31 LSNKVALVTASTDGIGFAIARRLAEDGAHVVVSSRKQQNVDRAVATLQGEGLSVTGIVCHVGKAEDREKLITTALKRHQG 110
Cdd:PRK12939    5 LAGKRALVTGAARGLGAAFAEALAEAGATVAFNDGLAAEARELAAALEAAGGRAHAIAADLADPASVQRFFDAAAAALGG 84

                          90       100
                  ....*....|....*....|....*..
gi 1720379773 111 IDILVSNAAVNPfFGNLMDVTEEVWDK 137
Cdd:PRK12939   85 LDGLVNNAGITN-SKSATELDIDTWDA 110

Polyketide ketoreductase, classical (c) SDR; Polyketide ketoreductase (KR) is a classical SDR with a characteristic NAD-binding pattern and active site tetrad. Aromatic polyketides include various aromatic compounds of pharmaceutical interest. Polyketide KR, part of the type II polyketide synthase (PKS) complex, is comprised of stand-alone domains that resemble the domains found in fatty acid synthase and multidomain type I PKS. 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 1720379773  33 NKVALVTASTDGIGFAIARRLAEDGAHVVVSSRKQQNVDRAVATLQGEGLSVTGIVCHVGKAEDREKLITTALKRHQGID 112
Cdd:cd08945     3 SEVALVTGATSGIGLAIARRLGKEGLRVFVCARGEEGLATTVKELREAGVEADGRTCDVRSVPEIEALVAAAVARYGPID 82

                          90       100
                  ....*....|....*....|....
gi 1720379773 113 ILVSNAAvNPFFGNLMDVTEEVWD 136
Cdd:cd08945    83 VLVNNAG-RSGGGATAELADELWL 105

SDR family oxidoreductase;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720379773  31 LSNKVALVTASTDGIGFAIARRLAEDGAHVVVSSRKQQNVDRAVATLQGEGLSVTGIVCHVGKAEDREKLITTALKRHQG 110
Cdd:PRK06124    9 LAGQVALVTGSARGLGFEIARALAGAGAHVLVNGRNAATLEAAVAALRAAGGAAEALAFDIADEEAVAAAFARIDAEHGR 88

                  ....*...
gi 1720379773 111 IDILVSNA 118
Cdd:PRK06124   89 LDILVNNV 96

short chain dehydrogenase; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720379773  30 PLSNKVALVTASTDGIGFAIARRLAEDGAHVVVSSRKQQNVDRAVATLQGEGLsvtGIVCHVGKAEDREKLITTALKRHQ 109
Cdd:PRK06841   12 DLSGKVAVVTGGASGIGHAIAELFAAKGARVALLDRSEDVAEVAAQLLGGNAK---GLVCDVSDSQSVEAAVAAVISAFG 88

                          90       100
                  ....*....|....*....|....*...
gi 1720379773 110 GIDILVSNAAVNPfFGNLMDVTEEVWDK 137
Cdd:PRK06841   89 RIDILVNSAGVAL-LAPAEDVSEEDWDK 115

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720379773  40 ASTDGIGFAIARRLAEDGAHVVVS--SRKQQNVDRAVATLQGEGLsvtgIVCHVGKAEDREKLITTALKRHQGIDILVSN 117
Cdd:pfam13561   3 ANESGIGWAIARALAEEGAEVVLTdlNEALAKRVEELAEELGAAV----LPCDVTDEEQVEALVAAAVEKFGRLDILVNN 78

                          90       100
                  ....*....|....*....|.
gi 1720379773 118 AAV-NPFFGNLMDVTEEVWDK 137
Cdd:pfam13561  79 AGFaPKLKGPFLDTSREDFDR 99

tropinone reductase-I and II (TR-1, and TR-II)-like, classical (c) SDRs; This subgroup includes TR-I and TR-II; these proteins are members of the SDR family. TRs catalyze the NADPH-dependent reductions of the 3-carbonyl group of tropinone, to a beta-hydroxyl group. TR-I and TR-II produce different stereoisomers from tropinone, TR-I produces tropine (3alpha-hydroxytropane), and TR-II, produces pseudotropine (sigma-tropine, 3beta-hydroxytropane). SDRs are a functionally diverse family of oxidoreductases that have a single domain with a structurally conserved Rossmann fold (alpha/beta folding pattern with a central beta-sheet), an NAD(P)(H)-binding region, and a structurally diverse C-terminal region. Classical SDRs are typically about 250 residues long, while extended SDRs are approximately 350 residues. Sequence identity between different SDR enzymes are typically in the 15-30% range, but the enzymes share the Rossmann fold NAD-binding motif and characteristic NAD-binding and catalytic sequence patterns. These enzymes catalyze a wide range of activities including the metabolism of steroids, cofactors, carbohydrates, lipids, aromatic compounds, and amino acids, and act in redox sensing. Classical SDRs have an TGXXX[AG]XG cofactor binding motif and a YXXXK active site motif, with the Tyr residue of the active site motif serving as a critical catalytic residue (Tyr-151, human 15-hydroxyprostaglandin dehydrogenase (15-PGDH) numbering). In addition to the Tyr and Lys, there is often an upstream Ser (Ser-138, 15-PGDH numbering) and/or an Asn (Asn-107, 15-PGDH numbering) contributing to the active site; while substrate binding is in the C-terminal region, which determines specificity. The standard reaction mechanism is a 4-pro-S hydride transfer and proton relay involving the conserved Tyr and Lys, a water molecule stabilized by Asn, and nicotinamide. Extended SDRs have additional elements in the C-terminal region, and typically have a TGXXGXXG cofactor binding motif. Complex (multidomain) SDRs such as ketoreductase domains of fatty acid synthase have a GGXGXXG NAD(P)-binding motif and an altered active site motif (YXXXN). Fungal type ketoacyl reductases have a TGXXXGX(1-2)G NAD(P)-binding motif. Some atypical SDRs have lost catalytic activity and/or have an unusual NAD(P)-binding motif and missing or unusual active site residues. Reactions catalyzed within the SDR family include isomerization, decarboxylation, epimerization, C=N bond reduction, dehydratase activity, dehalogenation, Enoyl-CoA reduction, and carbonyl-alcohol oxidoreduction.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720379773  31 LSNKVALVTASTDGIGFAIARRLAEDGAHVVVSSRKQQNVDRAVATLQGEGLSVTGIVCHVGKAEDREKLITTALKRHQG 110
Cdd:cd05329     4 LEGKTALVTGGTKGIGYAIVEELAGLGAEVYTCARNQKELDECLTEWREKGFKVEGSVCDVSSRSERQELMDTVASHFGG 83

                          90       100
                  ....*....|....*....|....*.
gi 1720379773 111 -IDILVSNAAVNpFFGNLMDVTEEVW 135
Cdd:cd05329    84 kLNILVNNAGTN-IRKEAKDYTEEDY 108

short chain dehydrogenase; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720379773  31 LSNKVALVTASTDGIGFAIARRLAEDGA-HVVVSSRKQQNVDRAVATLQGEGLSVTGIVCHVGKAEDREKLITTALKRHQ 109
Cdd:PRK06198    4 LDGKVALVTGGTQGLGAAIARAFAERGAaGLVICGRNAEKGEAQAAELEALGAKAVFVQADLSDVEDCRRVVAAADEAFG 83

                          90       100
                  ....*....|....*....|....*...
gi 1720379773 110 GIDILVsNAAVNPFFGNLMDVTEEVWDK 137
Cdd:PRK06198   84 RLDALV-NAAGLTDRGTILDTSPELFDR 110

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 1720379773  31 LSNKVALVTASTDGIGFAIARRLAEDGAHVVVSSRKQQnvDRAVATLQ------GEGLSVTGivcHVGKAEDREKLITTA 104
Cdd:cd05358     1 LKGKVALVTGASSGIGKAIAIRLATAGANVVVNYRSKE--DAAEEVVEeikavgGKAIAVQA---DVSKEEDVVALFQSA 75

                          90       100       110
                  ....*....|....*....|....*....|....*
gi 1720379773 105 LKRHQGIDILVSNAAVNpffGNLM--DVTEEVWDK 137
Cdd:cd05358    76 IKEFGTLDILVNNAGLQ---GDASshEMTLEDWNK 107

rhamnulose-1-phosphate aldolase/alcohol dehydrogenase, classical (c) SDRs; This family has bifunctional proteins with an N-terminal aldolase and a C-terminal classical SDR domain. One member is identified as a rhamnulose-1-phosphate aldolase/alcohol dehydrogenase. The SDR domain has a canonical SDR glycine-rich NAD(P) binding motif and a match to the characteristic active site triad. However, it lacks an upstream active site Asn typical of 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 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 1720379773  34 KVALVTASTDGIGFAIARRLAEDGAHVVVSSRKQQNVDRAVATLQGeGLSVTGIVCHVGKAEDREKLITTALKRHQGIDI 113
Cdd:cd08943     2 KVALVTGGASGIGLAIAKRLAAEGAAVVVADIDPEIAEKVAEAAQG-GPRALGVQCDVTSEAQVQSAFEQAVLEFGGLDI 80

                          90       100
                  ....*....|....*....|....
gi 1720379773 114 LVSNAAVNPfFGNLMDVTEEVWDK 137
Cdd:cd08943    81 VVSNAGIAT-SSPIAETSLEDWNR 103

human dehydrogenase/reductase (SDR family) member 1 (DHRS1) and human hydroxysteroid dehydrogenase-like protein 2 (HSDL2), classical (c) SDRs; This subgroup includes human DHRS1 and human HSDL2 and related proteins. These are members of the classical SDR family, with a canonical Gly-rich NAD-binding motif and the typical YXXXK active site motif. However, the rest of the catalytic tetrad is not strongly conserved. DHRS1 mRNA has been detected in many tissues, liver, heart, skeletal muscle, kidney and pancreas; a longer transcript is predominantly expressed in the liver , a shorter one in the heart. HSDL2 may play a part in fatty acid metabolism, as it is found in peroxisomes. 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 1720379773  31 LSNKVALVTASTDGIGFAIARRLAEDGAHVVVSSRKQQNVD------------RAVATLQGEGLSVTGIVCHVGKAEDRE 98
Cdd:cd05338     1 LSGKVAFVTGASRGIGRAIALRLAKAGATVVVAAKTASEGDngsakslpgtieETAEEIEAAGGQALPIVVDVRDEDQVR 80

                          90       100       110
                  ....*....|....*....|....*....|....*...
gi 1720379773  99 KLITTALKRHQGIDILVSNAAVNpFFGNLMDVTEEVWD 136
Cdd:cd05338    81 ALVEATVDQFGRLDILVNNAGAI-WLSLVEDTPAKRFD 117

short chain dehydrogenase; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720379773  30 PLSNKVALVTASTDGIGFAIARRLAEDGAHVVVS-SRKQQNVDRAVATLQGEGLSVTGIVCHVGKAEDREKLITTALKRH 108
Cdd:PRK12937    2 TLSNKVAIVTGASRGIGAAIARRLAADGFAVAVNyAGSAAAADELVAEIEAAGGRAIAVQADVADAAAVTRLFDAAETAF 81

                          90       100
                  ....*....|....*....|....*....
gi 1720379773 109 QGIDILVSNAAVNPfFGNLMDVTEEVWDK 137
Cdd:PRK12937   82 GRIDVLVNNAGVMP-LGTIADFDLEDFDR 109

SDR family oxidoreductase;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720379773  26 TRRNPLSNKVALVTASTDGIGFAIARRLAEDGAHVVVSSRKQQNVDRAVATLQGEGLSVTGIVCHVGKAEDREKLITTAL 105
Cdd:PRK07201  364 DLRGPLVGKVVLITGASSGIGRATAIKVAEAGATVFLVARNGEALDELVAEIRAKGGTAHAYTCDLTDSAAVDHTVKDIL 443

                          90
                  ....*....|...
gi 1720379773 106 KRHQGIDILVSNA 118
Cdd:PRK07201  444 AEHGHVDYLVNNA 456

classical (c) SDR, subgroup 4; This subgroup has 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 1720379773  34 KVALVTASTDGIGFAIARRLAEDGAHVVVSSRKQQNVDRAVATLQGeglSVTGIVCHVGKAEDREKLITTALKRHQGIDI 113
Cdd:cd08929     1 KAALVTGASRGIGEATARLLHAEGYRVGICARDEARLAAAAAQELE---GVLGLAGDVRDEADVRRAVDAMEEAFGGLDA 77

                          90       100
                  ....*....|....*....|..
gi 1720379773 114 LVSNAAVNpFFGNLMDVTEEVW 135
Cdd:cd08929    78 LVNNAGVG-VMKPVEELTPEEW 98

short chain dehydrogenase; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720379773  31 LSNKVALVTASTDGIGFAIARRLAEDGAHVVVSSRKQQNVDRAVATLQGEGLSVTGIVCHVGKAEDREKLITTALKRHQG 110
Cdd:PRK07576    7 FAGKNVVVVGGTSGINLGIAQAFARAGANVAVASRSQEKVDAAVAQLQQAGPEGLGVSADVRDYAAVEAAFAQIADEFGP 86

                          90
                  ....*....|.
gi 1720379773 111 IDILVSNAAVN 121
Cdd:PRK07576   87 IDVLVSGAAGN 97

short chain dehydrogenase; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720379773  31 LSNKVALVTASTDGIGFAIARRLAEDGAHVVVSSRKQQNVDRAVATLQGEGLSVTGIVCHVGKAEDREKLITTALKRHQG 110
Cdd:PRK07890    3 LKGKVVVVSGVGPGLGRTLAVRAARAGADVVLAARTAERLDEVAAEIDDLGRRALAVPTDITDEDQCANLVALALERFGR 82