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 372626410   1 MSKQNGGEGGIIINMSSLAGLMPVAQQPVYCASKHGIVGFTRSAALAANlMNSGVRLNAICPGFVNTAILESIEKEEnmg 80
Cdd:cd05323  125 MDKNKGGKGGVIVNIGSVAGLYPAPQFPVYSASKHGVVGFTRSLADLLE-YKTGVRVNAICPGFTNTPLLPDLVAKE--- 200

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|...
gi 372626410  81 qyieykdhiKDMIKYYGILDPPLIANGLITLIEDDALNGAIMKITTSKGIHFQ 133
Cdd:cd05323  201 ---------AEMLPSAPTQSPEVVAKAIVYLIEDDEKNGAIWIVDGGKLIEIE 244

insect type alcohol dehydrogenase (ADH)-like, classical (c) SDRs; This subgroup contains insect type ADH, and 15-hydroxyprostaglandin dehydrogenase (15-PGDH) type I; these proteins are classical SDRs. ADH catalyzes the NAD+-dependent oxidation of alcohols to aldehydes/ketones. This subgroup is distinct from the zinc-dependent alcohol dehydrogenases of the medium chain dehydrogenase/reductase family, and evolved in fruit flies to allow the digestion of fermenting fruit. 15-PGDH catalyzes the NAD-dependent interconversion of (5Z,13E)-(15S)-11alpha,15-dihydroxy-9-oxoprost-13-enoate and (5Z,13E)-11alpha-hydroxy-9,15-dioxoprost-13-enoate, and has a typical SDR glycine-rich NAD-binding motif, which is not fully present in ADH. 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 372626410   1 MSKQNGGEGGIIINMSSLAGLMPVAQQPVYCASKHGIVGFTRSAALAANlMNSGVRLNAICPGFVNTAILESIEKEEnmg 80
Cdd:cd05323  125 MDKNKGGKGGVIVNIGSVAGLYPAPQFPVYSASKHGVVGFTRSLADLLE-YKTGVRVNAICPGFTNTPLLPDLVAKE--- 200

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|...
gi 372626410  81 qyieykdhiKDMIKYYGILDPPLIANGLITLIEDDALNGAIMKITTSKGIHFQ 133
Cdd:cd05323  201 ---------AEMLPSAPTQSPEVVAKAIVYLIEDDEKNGAIWIVDGGKLIEIE 244

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 372626410   1 MSKQnggEGGIIINMSSLAGLMPVAQQPVYCASKHGIVGFTRSaaLAANLMNSGVRLNAICPGFVNTAILESIEKEENMG 80
Cdd:COG1028  129 MRER---GGGRIVNISSIAGLRGSPGQAAYAASKAAVVGLTRS--LALELAPRGIRVNAVAPGPIDTPMTRALLGAEEVR 203

                 ...
gi 372626410  81 QYI 83
Cdd:COG1028  204 EAL 206

pteridine reductase; Pteridine reductase is an enzyme used by trypanosomatids (including Trypanosoma cruzi and Leishmania major) to obtain reduced pteridines by salvage rather than biosynthetic pathways. Enzymes in T. cruzi described as pteridine reductase 1 (PTR1) and pteridine reductase 2 (PTR2) have different activity profiles. PTR1 is more active with with fully oxidized biopterin and folate than with reduced forms, while PTR2 reduces dihydrobiopterin and dihydrofolate but not oxidized pteridines. T. cruzi PTR1 and PTR2 are more similar to each other in sequence than either is to the pteridine reductase of Leishmania major, and all are included in this family.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 372626410   12 IINMSSLAGLMPVAQQPVYCASKHGIVGFTRSAALaaNLMNSGVRLNAICPG 63
Cdd:TIGR02685 155 IVNLCDAMTDQPLLGFTMYTMAKHALEGLTRSAAL--ELAPLQIRVNGVAPG 204

insect type alcohol dehydrogenase (ADH)-like, classical (c) SDRs; This subgroup contains insect type ADH, and 15-hydroxyprostaglandin dehydrogenase (15-PGDH) type I; these proteins are classical SDRs. ADH catalyzes the NAD+-dependent oxidation of alcohols to aldehydes/ketones. This subgroup is distinct from the zinc-dependent alcohol dehydrogenases of the medium chain dehydrogenase/reductase family, and evolved in fruit flies to allow the digestion of fermenting fruit. 15-PGDH catalyzes the NAD-dependent interconversion of (5Z,13E)-(15S)-11alpha,15-dihydroxy-9-oxoprost-13-enoate and (5Z,13E)-11alpha-hydroxy-9,15-dioxoprost-13-enoate, and has a typical SDR glycine-rich NAD-binding motif, which is not fully present in ADH. 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 372626410   1 MSKQNGGEGGIIINMSSLAGLMPVAQQPVYCASKHGIVGFTRSAALAANlMNSGVRLNAICPGFVNTAILESIEKEEnmg 80
Cdd:cd05323  125 MDKNKGGKGGVIVNIGSVAGLYPAPQFPVYSASKHGVVGFTRSLADLLE-YKTGVRVNAICPGFTNTPLLPDLVAKE--- 200

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|...
gi 372626410  81 qyieykdhiKDMIKYYGILDPPLIANGLITLIEDDALNGAIMKITTSKGIHFQ 133
Cdd:cd05323  201 ---------AEMLPSAPTQSPEVVAKAIVYLIEDDEKNGAIWIVDGGKLIEIE 244

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

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 372626410    6 GGEGGIIINMSSLAGLMPVAQQPVYCASKHGIVGFTRSaaLAANLMNSGVRLNAICPGFVNTAILESIEKEEN 78
Cdd:pfam00106 125 KGSGGRIVNISSVAGLVPYPGGSAYSASKAAVIGFTRS--LALELAPHGIRVNAVAPGGVDTDMTKELREDEG 195

Short-chain dehydrogenase [General function prediction only];

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 372626410   9 GGIIINMSSLAGLMPVAQQPVYCASKHGIVGFTRSaaLAANLMNSGVRLNAICPGFVNTAILE 71
Cdd:COG0300  133 RGRIVNVSSVAGLRGLPGMAAYAASKAALEGFSES--LRAELAPTGVRVTAVCPGPVDTPFTA 193

3-oxoacyl-ACP reductase FabG;

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 372626410   1 MSKQNGGEggiIINMSSLAGLMPVAQQPVYCASKHGIVGFTRsaALAANLMNSGVRLNAICPGFVNTAILESIEKeenmg 80
Cdd:PRK05653 128 MIKARYGR---IVNISSVSGVTGNPGQTNYSAAKAGVIGFTK--ALALELASRGITVNAVAPGFIDTDMTEGLPE----- 197

                         90
                 ....*....|...
gi 372626410  81 qyiEYKDHIKDMI 93
Cdd:PRK05653 198 ---EVKAEILKEI 207

short chain dehydrogenase; Provisional

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 372626410  10 GIIINMSSLAGLMPVAQQPVYCASKHGIVGFTrsAALAANLMNSGVRLNAICPGFVNT 67
Cdd:PRK07825 130 GHVVNVASLAGKIPVPGMATYCASKHAVVGFT--DAARLELRGTGVHVSVVLPSFVNT 185

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 372626410   1 MSKQNGGEggiIINMSSLAGLMPVAQQPVYCASKHGIVGFTRSAALAAnlMNSGVRLNAICPGFVNTAILE 71
Cdd:cd08940  127 MKKQGWGR---IINIASVHGLVASANKSAYVAAKHGVVGLTKVVALET--AGTGVTCNAICPGWVLTPLVE 192

3beta17beta hydroxysteroid dehydrogenase-like, classical (c) SDRs; This subgroup includes members identified as 3beta17beta hydroxysteroid dehydrogenase, 20beta hydroxysteroid dehydrogenase, and R-alcohol dehydrogenase. These proteins exhibit the canonical active site tetrad and glycine rich NAD(P)-binding motif of the classical SDRs. 17beta-dehydrogenases are a group of isozymes that catalyze activation and inactivation of estrogen and androgens, and include members of the SDR family. 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 372626410   9 GGIIINMSSLAGLMPVAQQPVYCASKHGIVGFTRSAALAANLMNSGVRLNAICPGFVNTAIL-ESIEKEENMGQYIEYKD 87
Cdd:cd05341  130 GGSIINMSSIEGLVGDPALAAYNASKGAVRGLTKSAALECATQGYGIRVNSVHPGYIYTPMTdELLIAQGEMGNYPNTPM 209

                         90       100       110
                 ....*....|....*....|....*....|....*
gi 372626410  88 HikdmikyyGILDPPLIANGLITLIEDDA--LNGA 120
Cdd:cd05341  210 G--------RAGEPDEIAYAVVYLASDESsfVTGS 236

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 372626410  10 GIIINMSSLAGLMPVAQQPVYCASKHGIVGFTRSaaLAANLMNSGVRLNAICPGFVNTAILESIEKeenmgqyiEYKDHI 89
Cdd:cd05333  129 GRIINISSVVGLIGNPGQANYAASKAGVIGFTKS--LAKELASRGITVNAVAPGFIDTDMTDALPE--------KVKEKI 198

                         90       100
                 ....*....|....*....|....*....
gi 372626410  90 KDMI--KYYGilDPPLIANGLITLIEDDA 116
Cdd:cd05333  199 LKQIplGRLG--TPEEVANAVAFLASDDA 225

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 372626410   9 GGIIINMSSLAGLMPVAQQPVYCASKHGIVGFTRsaALAANLMNSGVRLNAICPGFVNTAILESIEKEEnmgqyieyKDH 88
Cdd:PRK05565 134 SGVIVNISSIWGLIGASCEVLYSASKGAVNAFTK--ALAKELAPSGIRVNAVAPGAIDTEMWSSFSEED--------KEG 203

                         90       100       110
                 ....*....|....*....|....*....|....*...
gi 372626410  89 IKDMIKYYGILDPPLIANGLITLIEDDA--LNGAIMKI 124
Cdd:PRK05565 204 LAEEIPLGRLGKPEEIAKVVLFLASDDAsyITGQIITV 241

3-oxoacyl-ACP reductase;

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 372626410   1 MSKQNGGEggiIINMSSLAGLMPVAQQPVYCASKHGIVGFTRsaALAANLMNSGVRLNAICPGFVNTAILESIEKEENmg 80
Cdd:PRK12824 126 MCEQGYGR---IINISSVNGLKGQFGQTNYSAAKAGMIGFTK--ALASEGARYGITVNCIAPGYIATPMVEQMGPEVL-- 198

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*.
gi 372626410  81 qyieykDHIKDMIKYYGILDPPLIANGLITLIEDDA--LNGAIMKI 124
Cdd:PRK12824 199 ------QSIVNQIPMKRLGTPEEIAAAVAFLVSEAAgfITGETISI 238

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 372626410   1 MSKQNGGEggiIINMSSLAGLMP-VAQQPVYCASKHGIVGFTRSaaLAANLMNSGVRLNAICPGFVNTAILESIekeenM 79
Cdd:cd05368  116 MLARKDGS---IINMSSVASSIKgVPNRFVYSTTKAAVIGLTKS--VAADFAQQGIRCNAICPGTVDTPSLEER-----I 185

                         90
                 ....*....|....*
gi 372626410  80 GQYIEYKDHIKDMIK 94
Cdd:cd05368  186 QAQPDPEEALKAFAA 200

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

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 372626410   1 MSKQNGGEggiIINMSSLAGLMPVAQQPVYCASKHGIVGFTRSAALaaNLMNSGVRLNAICPGFVNTAILESIEKEE 77
Cdd:PRK12825 130 MRKQRGGR---IVNISSVAGLPGWPGRSNYAAAKAGLVGLTKALAR--ELAEYGITVNMVAPGDIDTDMKEATIEEA 201

short chain dehydrogenase; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 372626410   6 GGEGGIIINMSSLAGLMPVAQQPVYCASKHGIVGFTRSaaLAANLMNSGVRLNAICPGFVNTAILESI---------EKE 76
Cdd:PRK12829 136 SGHGGVIIALSSVAGRLGYPGRTPYAASKWAVVGLVKS--LAIELGPLGIRVNAILPGIVRGPRMRRViearaqqlgIGL 213

                         90
                 ....*....|...
gi 372626410  77 ENMGQyiEYKDHI 89
Cdd:PRK12829 214 DEMEQ--EYLEKI 224

L-iditol 2-dehydrogenase;

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 372626410   7 GEGGIIINMSSLAGLMPVAQQPVYCASKHGIVGFTRSAALAanLMNSGVRLNAICPGFVNT 67
Cdd:PRK07067 130 GRGGKIINMASQAGRRGEALVSHYCATKAAVISYTQSAALA--LIRHGINVNAIAPGVVDT 188

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

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 372626410  10 GIIINMSSLAGLMPVAQQPVYCASKHGIVGFTRSaaLAANLMNSGVRLNAICPGFVNTA 68
Cdd:PRK06550 120 GIIINMCSIASFVAGGGGAAYTASKHALAGFTKQ--LALDYAKDGIQVFGIAPGAVKTP 176

SDR family oxidoreductase;

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 372626410   9 GGIIINMSSLAGLMPVAQQPVYCASKHGIVGFTRsaALAANLMNSGVRLNAICPGFVNTAILES 72
Cdd:PRK07454 134 GGLIINVSSIAARNAFPQWGAYCVSKAALAAFTK--CLAEEERSHGIRVCTITLGAVNTPLWDT 195

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

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 372626410   2 SKQNGGE-GGIIINMSSLAGLMPVAQQPVYCASKHGIVGFTRSAALAanLMNSGVRLNAICP 62
Cdd:PRK07792 139 AKAAGGPvYGRIVNTSSEAGLVGPVGQANYGAAKAGITALTLSAARA--LGRYGVRANAICP 198

pteridine reductase (PR), classical (c) SDRs; Pteridine reductases (PRs), members of the SDR family, catalyzes the NAD-dependent reduction of folic acid, dihydrofolate and related compounds. In Leishmania, pteridine reductase (PTR1) acts to circumvent the anti-protozoan drugs that attack dihydrofolate reductase activity. Proteins in this subgroup have an N-terminal NAD-binding motif and a YxxxK active site motif, but have an Asp instead of the usual upstream catalytic Ser. 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 372626410   6 GGEGGIIINMSSLAGLMPVAQQPVYCASKHGIVGFTRSAA--LAANlmnsgVRLNAICPGFVNtailesiekeENMGQYI 83
Cdd:cd05357  126 GSRNGSIINIIDAMTDRPLTGYFAYCMSKAALEGLTRSAAleLAPN-----IRVNGIAPGLIL----------LPEDMDA 190

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|.
gi 372626410  84 EYKDHIKDMIKYYGILDPPLIANGLITLIEDDALNGAIMKI 124
Cdd:cd05357  191 EYRENALRKVPLKRRPSAEEIADAVIFLLDSNYITGQIIKV 231

acetoacetyl-CoA reductase; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 372626410   8 EGGIIINMSSLAGLMPVAQQPVYCASKHGIVGFTRSaaLAANLMNSGVRLNAICPGFVNTAILESIEKEenmgqyIEYKD 87
Cdd:PRK12935 134 EEGRIISISSIIGQAGGFGQTNYSAAKAGMLGFTKS--LALELAKTNVTVNAICPGFIDTEMVAEVPEE------VRQKI 205

                         90       100
                 ....*....|....*....|....*....
gi 372626410  88 HIKDMIKYYGILDPplIANGLITLIEDDA 116
Cdd:PRK12935 206 VAKIPKKRFGQADE--IAKGVVYLCRDGA 232

cyclohexanol reductases, including levodione reductase, classical (c) SDRs; Cyloclohexanol reductases,including (6R)-2,2,6-trimethyl-1,4-cyclohexanedione (levodione) reductase of Corynebacterium aquaticum, catalyze the reversible oxidoreduction of hydroxycyclohexanone derivatives. 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 372626410  10 GIIINMSSLAGLMPVAQQPVYCASKHGIVGFTRSAALAANlmNSGVRLNAICPGFVNTAILESIEK-------EENMGQY 82
Cdd:cd05330  135 GMIVNTASVGGIRGVGNQSGYAAAKHGVVGLTRNSAVEYG--QYGIRINAIAPGAILTPMVEGSLKqlgpenpEEAGEEF 212

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....
gi 372626410  83 IEYkdhikDMIKYYGilDPPLIANGLITLIEDDA--LNGAIMKI 124
Cdd:cd05330  213 VSV-----NPMKRFG--EPEEVAAVVAFLLSDDAgyVNAAVVPI 249

Sorbitol dehydrogenase (SDH), classical (c) SDR; This bacterial subgroup includes Rhodobacter sphaeroides SDH, and other SDHs. SDH preferentially interconverts D-sorbitol (D-glucitol) and D-fructose, but also interconverts L-iditol/L-sorbose and galactitol/D-tagatose. SDH is NAD-dependent and is a dimeric member of the SDR family. 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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 372626410   6 GGEGGIIINMSSLAGLMPVAQQPVYCASKHGIVGFTRSAALaaNLMNSGVRLNAICPGFVNTAILESIE 74
Cdd:cd05363  126 QGRGGKIINMASQAGRRGEALVGVYCATKAAVISLTQSAGL--NLIRHGINVNAIAPGVVDGEHWDGVD 192

(S)-acetoin forming diacetyl reductase;

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 372626410   7 GEGGIIINMSSLAGLMPVAQQPVYCASKHGIVGFTRSAalAANLMNSGVRLNAICPGFVNTAILESIEKE--ENMGQYIE 84
Cdd:PRK08643 129 GHGGKIINATSQAGVVGNPELAVYSSTKFAVRGLTQTA--ARDLASEGITVNAYAPGIVKTPMMFDIAHQvgENAGKPDE 206

                 .
gi 372626410  85 Y 85
Cdd:PRK08643 207 W 207

putative D-mannonate oxidoreductase, classical (c) SDR; D-mannonate oxidoreductase catalyzes the NAD-dependent interconversion of D-mannonate and D-fructuronate. This subgroup includes Bacillus subtitils UxuB/YjmF, a putative D-mannonate oxidoreductase; the B. subtilis UxuB gene is part of a putative ten-gene operon (the Yjm operon) involved in hexuronate catabolism. Escherichia coli UxuB does not belong to this subgroup. 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
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 372626410   6 GGEGGIIINMSSLAGLMPVAQQPVYCASKHGIVGFTRSaaLAANLMNSGVRLNAICPGFVNTA 68
Cdd:cd08935  144 EQKGGSIINISSMNAFSPLTKVPAYSAAKAAVSNFTQW--LAVEFATTGVRVNAIAPGFFVTP 204

SDR family oxidoreductase;

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 372626410   9 GGIIINMSSLAGLMPVAQQPVYCASKHGIVGFTRsaALAANLMNSGVRLNAICPGFVNTAI 69
Cdd:PRK06949 145 GGRIINIASVAGLRVLPQIGLYCMSKAAVVHMTR--AMALEWGRHGINVNAICPGYIDTEI 203

classical (c) SDR, subgroup 12; These are classical SDRs, with the canonical active site tetrad and glycine-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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 372626410   9 GGIIINMSSLAGLMPVAQQPVYCASKHGIVGFTRSaaLAANLMNSGVRLNAICPGFVNTAILES 72
Cdd:cd08944  129 GGSIVNLSSIAGQSGDPGYGAYGASKAAIRNLTRT--LAAELRHAGIRCNALAPGLIDTPLLLA 190

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 372626410   1 MSKQNGGEggiIINMSSLAGLMPVAQQPVYCASKHGIVGFTRsaALAANLMNSGVRLNAICPGFVNTAILESIEKEENMG 80
Cdd:PRK06935 137 MAKQGSGK---IINIASMLSFQGGKFVPAYTASKHGVAGLTK--AFANELAAYNIQVNAIAPGYIKTANTAPIRADKNRN 211

                 ...
gi 372626410  81 QYI 83
Cdd:PRK06935 212 DEI 214

SDR family oxidoreductase;

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 372626410   9 GGIIINMSSLAGLMPVAQQPVYCASKHGIVGFTRSAALaaNLMNSGVRLNAICPGFVNT 67
Cdd:PRK07326 132 GGYIINISSLAGTNFFAGGAAYNASKFGLVGFSEAAML--DLRQYGIKVSTIMPGSVAT 188

classical (c) SDR, subgroup 9; This subgroup has the canonical active site tetrad and 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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 372626410   9 GGIIINMSSLAGLMPVAQQPVYCASKHGIVGFTRsaALAANLMNSGVRLNAICPGFVNTAILESIEKEENM 79
Cdd:cd08931  127 GARVINTASSSAIYGQPDLAVYSATKFAVRGLTE--ALDVEWARHGIRVADVWPWFVDTPILTKGETGAAP 195

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 372626410  10 GIIINMSSLAGLMPVAQQPVYCASKHGIVGFTRSaaLAANLMNSGVRLNAICPGFVNTAILESIEKEEnmgqyiEYKDHI 89
Cdd:cd05358  134 GKIINMSSVHEKIPWPGHVNYAASKGGVKMMTKT--LAQEYAPKGIRVNAIAPGAINTPINAEAWDDP------EQRADL 205

                         90       100
                 ....*....|....*....|....*..
gi 372626410  90 KDMIKYYGILDPPLIANGLITLIEDDA 116
Cdd:cd05358  206 LSLIPMGRIGEPEEIAAAAAWLASDEA 232

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 372626410   1 MSKQNGGEggiIINMSSL---AGLMPVaqqPVYCASKHGIVGFTRsaALAANLMNSGVRLNAICPGFVNTAILESIEKEE 77
Cdd:cd05347  128 MIKQGHGK---IINICSLlseLGGPPV---PAYAASKGGVAGLTK--ALATEWARHGIQVNAIAPGYFATEMTEAVVADP 199

                         90
                 ....*....|..
gi 372626410  78 NMGQYIEykDHI 89
Cdd:cd05347  200 EFNDDIL--KRI 209

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
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 372626410   9 GGIIINMSSLAGLMPVAQQPVYCASKHGIVGFtrSAALAANLMNSGVRLNAICPGFVNT 67
Cdd:cd05346  130 QGHIINLGSIAGRYPYAGGNVYCATKAAVRQF--SLNLRKDLIGTGIRVTNIEPGLVET 186