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 2444531563   8 ALVTGASSGIGAEYAAQLAARGHDLVLVARDAARLAALAARLGGAAGvaVEVLQADLTRPADVAAVGARL-AADPALRLL 86
Cdd:cd05233     1 ALVTGASSGIGRAIARRLAREGAKVVLADRNEEALAELAAIEALGGN--AVAVQADVSDEEDVEALVEEAlEEFGRLDIL 78

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2444531563  87 VNCAGLGPMGPVLPGPAAGYDPMVALNVTALQHLTLAAASAFAERGGGTIVNVSSVVALLPERFNAVYAASKAYVLALTQ 166
Cdd:cd05233    79 VNNAGIARPGPLEELTDEDWDRVLDVNLTGVFLLTRAALPHMKKQGGGRIVNISSVAGLRPLPGQAAYAASKAALEGLTR 158

                         170       180       190
                  ....*....|....*....|....*....|....*....
gi 2444531563 167 GLASELAPRGVRLQAVLPGITRTELFARAGADLDRIPAA 205
Cdd:cd05233   159 SLALELAPYGIRVNAVAPGLVDTPMLAKLGPEEAEKELA 197

3-oxoacyl-ACP reductase FabG;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2444531563   8 ALVTGASSGIGAEYAAQLAARGHDLVLVARDAARLAALAARLGGAAGVaVEVLQADLTRPADV-AAVGARLAADPALRLL 86
Cdd:PRK05653    8 ALVTGASRGIGRAIALRLAADGAKVVIYDSNEEAAEALAAELRAAGGE-ARVLVFDVSDEAAVrALIEAAVEAFGALDIL 86

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2444531563  87 VNCAGLGPMGPVLPGPAAGYDPMVALNVTALQHLTLAAASAFAERGGGTIVNVSSVVALLPERFNAVYAASKAYVLALTQ 166
Cdd:PRK05653   87 VNNAGITRDALLPRMSEEDWDRVIDVNLTGTFNVVRAALPPMIKARYGRIVNISSVSGVTGNPGQTNYSAAKAGVIGFTK 166

                         170       180
                  ....*....|....*....|....
gi 2444531563 167 GLASELAPRGVRLQAVLPGITRTE 190
Cdd:PRK05653  167 ALALELASRGITVNAVAPGFIDTD 190

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 2444531563    9 LVTGASSGIGAEYAAQLAARGH-DLVLV--ARDAARLAALAARLGGAAGVAVEVLQADLTRPADVAAVGARL-AADPALR 84
Cdd:smart00822   4 LITGGLGGLGRALARWLAERGArRLVLLsrSGPDAPGAAALLAELEAAGARVTVVACDVADRDALAAVLAAIpAVEGPLT 83

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2444531563   85 LLVNCAGLGPMGPVLPGPAAGYDPMVALNVTALQHLtlaaASAFAERGGGTIVNVSSVVALLPERFNAVYAASKAYVLAL 164
Cdd:smart00822  84 GVIHAAGVLDDGVLASLTPERFAAVLAPKAAGAWNL----HELTADLPLDFFVLFSSIAGVLGSPGQANYAAANAFLDAL 159

                   ..
gi 2444531563  165 TQ 166
Cdd:smart00822 160 AE 161

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 2444531563   1 MTQAHGK-ALVTGASSGIGAEYAAQLAARGHDLVLVARDAARLAALAARLGGAAGVaVEVLQADLTRPADVAAVGAR-LA 78
Cdd:COG1028     1 MTRLKGKvALVTGGSSGIGRAIARALAAEGARVVITDRDAEALEAAAAELRAAGGR-ALAVAADVTDEAAVEALVAAaVA 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2444531563  79 ADPALRLLVNCAGLGPMGPVLPGPAAGYDPMVALNVTALQHLTLAAASAFAERGGGTIVNVSSVVALLPERFNAVYAASK 158
Cdd:COG1028    80 AFGRLDILVNNAGITPPGPLEELTEEDWDRVLDVNLKGPFLLTRAALPHMRERGGGRIVNISSIAGLRGSPGQAAYAASK 159

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|
gi 2444531563 159 AYVLALTQGLASELAPRGVRLQAVLPGITRTELFARAGAD 198
Cdd:COG1028   160 AAVVGLTRSLALELAPRGIRVNAVAPGPIDTPMTRALLGA 199

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 2444531563   8 ALVTGASSGIGAEYAAQLAARGHDLVLVARDAARLAALAARLGGAAGvaVEVLQADLTRPADVAAVGARL-AADPALRLL 86
Cdd:cd05233     1 ALVTGASSGIGRAIARRLAREGAKVVLADRNEEALAELAAIEALGGN--AVAVQADVSDEEDVEALVEEAlEEFGRLDIL 78

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2444531563  87 VNCAGLGPMGPVLPGPAAGYDPMVALNVTALQHLTLAAASAFAERGGGTIVNVSSVVALLPERFNAVYAASKAYVLALTQ 166
Cdd:cd05233    79 VNNAGIARPGPLEELTDEDWDRVLDVNLTGVFLLTRAALPHMKKQGGGRIVNISSVAGLRPLPGQAAYAASKAALEGLTR 158

                         170       180       190
                  ....*....|....*....|....*....|....*....
gi 2444531563 167 GLASELAPRGVRLQAVLPGITRTELFARAGADLDRIPAA 205
Cdd:cd05233   159 SLALELAPYGIRVNAVAPGLVDTPMLAKLGPEEAEKELA 197

17beta hydroxysteroid dehydrogenase-like, classical (c) SDRs; 17beta-hydroxysteroid dehydrogenases are a group of isozymes that catalyze activation and inactivation of estrogen and androgens. SDRs are a functionally diverse family of oxidoreductases that have a single domain with a structurally conserved Rossmann fold (alpha/beta folding pattern with a central beta-sheet), an NAD(P)(H)-binding region, and a structurally diverse C-terminal region. Classical SDRs are typically about 250 residues long, while extended SDRs are approximately 350 residues. Sequence identity between different SDR enzymes are typically in the 15-30% range, but the enzymes share the Rossmann fold NAD-binding motif and characteristic NAD-binding and catalytic sequence patterns. These enzymes catalyze a wide range of activities including the metabolism of steroids, cofactors, carbohydrates, lipids, aromatic compounds, and amino acids, and act in redox sensing. Classical SDRs have an TGXXX[AG]XG cofactor binding motif and a YXXXK active site motif, with the Tyr residue of the active site motif serving as a critical catalytic residue (Tyr-151, human 15-hydroxyprostaglandin dehydrogenase (15-PGDH) numbering). In addition to the Tyr and Lys, there is often an upstream Ser (Ser-138, 15-PGDH numbering) and/or an Asn (Asn-107, 15-PGDH numbering) contributing to the active site; while substrate binding is in the C-terminal region, which determines specificity. The standard reaction mechanism is a 4-pro-S hydride transfer and proton relay involving the conserved Tyr and Lys, a water molecule stabilized by Asn, and nicotinamide. Extended SDRs have additional elements in the C-terminal region, and typically have a TGXXGXXG cofactor binding motif. Complex (multidomain) SDRs such as ketoreductase domains of fatty acid synthase have a GGXGXXG NAD(P)-binding motif and an altered active site motif (YXXXN). Fungal type ketoacyl reductases have a TGXXXGX(1-2)G NAD(P)-binding motif. Some atypical SDRs have lost catalytic activity and/or have an unusual NAD(P)-binding motif and missing or unusual active site residues. Reactions catalyzed within the SDR family include isomerization, decarboxylation, epimerization, C=N bond reduction, dehydratase activity, dehalogenation, Enoyl-CoA reduction, and carbonyl-alcohol oxidoreduction.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2444531563   8 ALVTGASSGIGAEYAAQLAARGHdLVLvarDAARLAALAARLGGAAGVAVEVLQADLTRPADV-AAVGARLAADPALRLL 86
Cdd:cd05374     3 VLITGCSSGIGLALALALAAQGY-RVI---ATARNPDKLESLGELLNDNLEVLELDVTDEESIkAAVKEVIERFGRIDVL 78

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2444531563  87 VNCAGLGPMGPVLPGPAAGYDPMVALNVTALQHLTLAAASAFAERGGGTIVNVSSVVALLPERFNAVYAASKAYVLALTQ 166
Cdd:cd05374    79 VNNAGYGLFGPLEETSIEEVRELFEVNVFGPLRVTRAFLPLMRKQGSGRIVNVSSVAGLVPTPFLGPYCASKAALEALSE 158

                         170       180
                  ....*....|....*....|....*....
gi 2444531563 167 GLASELAPRGVRLQAVLPGITRTELFARA 195
Cdd:cd05374   159 SLRLELAPFGIKVTIIEPGPVRTGFADNA 187

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2444531563   8 ALVTGASSGIGAEYAAQLAARGHDLVLVARDAARLAALAARLGGAAGVAVEVLQADLTRPADVAAVGARLAADP-ALRLL 86
Cdd:PRK12825    9 ALVTGAARGLGRAIALRLARAGADVVVHYRSDEEAAEELVEAVEALGRRAQAVQADVTDKAALEAAVAAAVERFgRIDIL 88

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2444531563  87 VNCAGLGPMGPVLPGPAAGYDPMVALNVTALQHLTLAAASAFAERGGGTIVNVSSVVALLPERFNAVYAASKAYVLALTQ 166
Cdd:PRK12825   89 VNNAGIFEDKPLADMSDDEWDEVIDVNLSGVFHLLRAVVPPMRKQRGGRIVNISSVAGLPGWPGRSNYAAAKAGLVGLTK 168

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|...
gi 2444531563 167 GLASELAPRGVRLQAVLPGITRTE----LFARA-GADLDRIPA 204
Cdd:PRK12825  169 ALARELAEYGITVNMVAPGDIDTDmkeaTIEEArEAKDAETPL 211

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 2444531563   8 ALVTGASSGIGAEYAAQLAARGHDLVLVARDAARLAALAARLGGAAGVAVEVLQADLT-RPADVAAVGARLAaDPALRLL 86
Cdd:cd05356     4 AVVTGATDGIGKAYAEELAKRGFNVILISRTQEKLDAVAKEIEEKYGVETKTIAADFSaGDDIYERIEKELE-GLDIGIL 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2444531563  87 VNCAGLGPMGPVLPG--PAAGYDPMVALNVTALQHLTLAAASAFAERGGGTIVNVSSVVALLPERFNAVYAASKAYVLAL 164
Cdd:cd05356    83 VNNVGISHSIPEYFLetPEDELQDIINVNVMATLKMTRLILPGMVKRKKGAIVNISSFAGLIPTPLLATYSASKAFLDFF 162

                         170       180
                  ....*....|....*....|....*..
gi 2444531563 165 TQGLASELAPRGVRLQAVLPGITRTEL 191
Cdd:cd05356   163 SRALYEEYKSQGIDVQSLLPYLVATKM 189

SDR family oxidoreductase;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2444531563   8 ALVTGASSGIGAEYAAQLAARGHDlVLVARDAARLAALAARLGGAAGVAVEVlQADLTRPADV-AAVGARLAADPALRLL 86
Cdd:PRK07231    8 AIVTGASSGIGEGIARRFAAEGAR-VVVTDRNEEAAERVAAEILAGGRAIAV-AADVSDEADVeAAVAAALERFGSVDIL 85

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2444531563  87 VNCAGLGPM-GPVLPGPAAGYDPMVALNVTALQHLTLAAASAFAERGGGTIVNVSSVVALLPERFNAVYAASKAYVLALT 165
Cdd:PRK07231   86 VNNAGTTHRnGPLLDVDEAEFDRIFAVNVKSPYLWTQAAVPAMRGEGGGAIVNVASTAGLRPRPGLGWYNASKGAVITLT 165

                         170       180
                  ....*....|....*....|....*...
gi 2444531563 166 QGLASELAPRGVRLQAVLPGITRTELFA 193
Cdd:PRK07231  166 KALAAELGPDKIRVNAVAPVVVETGLLE 193

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 2444531563   7 KALVTGASSGIGAEYAAQLAARGHDlVLVARDAARLAALAARLGGAAGVAVEVLQADLTRPADVAAVGARLAAD-PALRL 85
Cdd:cd05333     2 VALVTGASRGIGRAIALRLAAEGAK-VAVTDRSEEAAAETVEEIKALGGNAAALEADVSDREAVEALVEKVEAEfGPVDI 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2444531563  86 LVNCAGLGPMGPVLPGPAAGYDPMVALNVTALQHLTLAAASAFAERGGGTIVNVSSVVALLPERFNAVYAASKAYVLALT 165
Cdd:cd05333    81 LVNNAGITRDNLLMRMSEEDWDAVINVNLTGVFNVTQAVIRAMIKRRSGRIINISSVVGLIGNPGQANYAASKAGVIGFT 160

                         170       180
                  ....*....|....*....|....*.
gi 2444531563 166 QGLASELAPRGVRLQAVLPGITRTEL 191
Cdd:cd05333   161 KSLAKELASRGITVNAVAPGFIDTDM 186

HetN oxidoreductase-like, classical (c) SDR; This subgroup includes Anabaena sp. strain PCC 7120 HetN, a putative oxidoreductase involved in heterocyst differentiation, and related proteins. 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 2444531563   8 ALVTGASSGIGAEYAAQLAARGHDLVLVARDAARLAALAARLGGaagvaVEVLQADLTRPADVAAV--GARLAADPaLRL 85
Cdd:cd08932     3 ALVTGASRGIGIEIARALARDGYRVSLGLRNPEDLAALSASGGD-----VEAVPYDARDPEDARALvdALRDRFGR-IDV 76

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2444531563  86 LVNCAGLGPMGPVLPGPAAGYDPMVALNVTALQHLTLAAASAFAERGGGTIVNVSSVVALLPERFNAVYAASKAYVLALT 165
Cdd:cd08932    77 LVHNAGIGRPTTLREGSDAELEAHFSINVIAPAELTRALLPALREAGSGRVVFLNSLSGKRVLAGNAGYSASKFALRALA 156

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|..
gi 2444531563 166 QGLASELAPRGVRLQAVLPGITRTELFARAGADLDRIPAAMI 207
Cdd:cd08932   157 HALRQEGWDHGVRVSAVCPGFVDTPMAQGLTLVGAFPPEEMI 198

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 2444531563   8 ALVTGASSGIGAEYAAQLAARGHDLVLVARDAARLAALAARLGGAAGVAVEVLQADLTRPADVAAVGARLAAD-PALRLL 86
Cdd:cd05359     1 ALVTGGSRGIGKAIALRLAERGADVVINYRKSKDAAAEVAAEIEELGGKAVVVRADVSQPQDVEEMFAAVKERfGRLDVL 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2444531563  87 VNCAGLGPMGPVLPGPAAGYDPMVALNVTALQHLTLAAASAFAERGGGTIVNVSSVVALLPERFNAVYAASKAYVLALTQ 166
Cdd:cd05359    81 VSNAAAGAFRPLSELTPAHWDAKMNTNLKALVHCAQQAAKLMRERGGGRIVAISSLGSIRALPNYLAVGTAKAALEALVR 160

                         170       180
                  ....*....|....*....|....
gi 2444531563 167 GLASELAPRGVRLQAVLPGITRTE 190
Cdd:cd05359   161 YLAVELGPRGIRVNAVSPGVIDTD 184

short chain dehydrogenase; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2444531563   9 LVTGASSGIGAEYAAQLAARGHDLVlvardaARLAALAARLGGAAGVAVEVLQADLtrpADVAAVGARLAADPALRLLVN 88
Cdd:PRK07060   13 LVTGASSGIGRACAVALAQRGARVV------AAARNAAALDRLAGETGCEPLRLDV---GDDAAIRAALAAAGAFDGLVN 83

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2444531563  89 CAGLGPMGPVLPGPAAGYDPMVALNV-TALQHLTLAAASAFAERGGGTIVNVSSVVALLPERFNAVYAASKAYVLALTQG 167
Cdd:PRK07060   84 CAGIASLESALDMTAEGFDRVMAVNArGAALVARHVARAMIAAGRGGSIVNVSSQAALVGLPDHLAYCASKAALDAITRV 163

                         170       180       190
                  ....*....|....*....|....*....|.
gi 2444531563 168 LASELAPRGVRLQAVLPGITRTELFARAGAD 198
Cdd:PRK07060  164 LCVELGPHGIRVNSVNPTVTLTPMAAEAWSD 194

2-dehydro-3-deoxy-D-gluconate 5-dehydrogenase KduD;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2444531563   6 GK-ALVTGASSGIGAEYAAQLAARGHDLVLVARDAARLAALAARLGGAAGvaVEVLQADLTRPADV-AAVGARLAADPAL 83
Cdd:PRK06935   15 GKvAIVTGGNTGLGQGYAVALAKAGADIIITTHGTNWDETRRLIEKEGRK--VTFVQVDLTKPESAeKVVKEALEEFGKI 92

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2444531563  84 RLLVNCAGLGPMGPVLPGPAAGYDPMVALNVTALQHLTLAAASAFAERGGGTIVNVSSVVALLPERFNAVYAASKAYVLA 163
Cdd:PRK06935   93 DILVNNAGTIRRAPLLEYKDEDWNAVMDINLNSVYHLSQAVAKVMAKQGSGKIINIASMLSFQGGKFVPAYTASKHGVAG 172

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*...
gi 2444531563 164 LTQGLASELAPRGVRLQAVLPGITRTELFARAGAD-------LDRIPA 204
Cdd:PRK06935  173 LTKAFANELAAYNIQVNAIAPGYIKTANTAPIRADknrndeiLKRIPA 220

3-ketodihydrosphingosine reductase (KDSR) and related proteins, classical (c) SDR; These proteins include members identified as KDSR, ribitol type dehydrogenase, and others. The group shows strong conservation of the active site tetrad and glycine rich NAD-binding motif of the classical 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 2444531563   5 HGKALVTGASSGIGAEYAAQLAARGHDLVLV---ARDAARLAALAARLGGAAGVAVEVLQADLTRPADVAAVGARLAADP 81
Cdd:cd08939     1 GKHVLITGGSSGIGKALAKELVKEGANVIIVarsESKLEEAVEEIEAEANASGQKVSYISADLSDYEEVEQAFAQAVEKG 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2444531563  82 AL-RLLVNCAGLGPMGPVLPGPAAGYDPMVALNVTALQHLTLAAASAFAERGGGTIVNVSSVVALLPERFNAVYAASKAY 160
Cdd:cd08939    81 GPpDLVVNCAGISIPGLFEDLTAEEFERGMDVNYFGSLNVAHAVLPLMKEQRPGHIVFVSSQAALVGIYGYSAYCPSKFA 160

                         170       180       190
                  ....*....|....*....|....*....|....
gi 2444531563 161 VLALTQGLASELAPRGVRLQAVLPGITRTELFAR 194
Cdd:cd08939   161 LRGLAESLRQELKPYNIRVSVVYPPDTDTPGFEE 194

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2444531563  15 SGIGAEYAAQLAARGHDLVLVARDAARLAALAARLGGAAgvaVEVLQADLTRPADVAAVGARLAAD-PALRLLVNCAGLG 93
Cdd:pfam13561   6 SGIGWAIARALAEEGAEVVLTDLNEALAKRVEELAEELG---AAVLPCDVTDEEQVEALVAAAVEKfGRLDILVNNAGFA 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2444531563  94 P--MGPVLPGPAAGYDPMVALNVTALQHLTLAAASAFAErgGGTIVNVSSVVALLPERFNAVYAASKAYVLALTQGLASE 171
Cdd:pfam13561  83 PklKGPFLDTSREDFDRALDVNLYSLFLLAKAALPLMKE--GGSIVNLSSIGAERVVPNYNAYGAAKAALEALTRYLAVE 160

                         170       180
                  ....*....|....*....|
gi 2444531563 172 LAPRGVRLQAVLPGITRTEL 191
Cdd:pfam13561 161 LGPRGIRVNAISPGPIKTLA 180

2,3-dihydroxybenzoate-2,3-dehydrogenase; Validated

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2444531563   1 MTQAHGKALVTGASSGIGAEYAAQLAARGHDLVLVARDAARLAALAarlggaagvaVEVLQADLTRPADVAAVGARLAAD 80
Cdd:PRK08220    4 MDFSGKTVWVTGAAQGIGYAVALAFVEAGAKVIGFDQAFLTQEDYP----------FATFVLDVSDAAAVAQVCQRLLAE 73

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2444531563  81 -PALRLLVNCAGLGPMGPVLPGPAAGYDPMVALNVTALQHLTLAAASAFAERGGGTIVNVSSVVALLPERFNAVYAASKA 159
Cdd:PRK08220   74 tGPLDVLVNAAGILRMGATDSLSDEDWQQTFAVNAGGAFNLFRAVMPQFRRQRSGAIVTVGSNAAHVPRIGMAAYGASKA 153

                         170       180       190
                  ....*....|....*....|....*....|..
gi 2444531563 160 YVLALTQGLASELAPRGVRLQAVLPGITRTEL 191
Cdd:PRK08220  154 ALTSLAKCVGLELAPYGVRCNVVSPGSTDTDM 185