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 530416654   1 MATGTRYAGKVVVVTGGGRGIGAGIVRAFVNSGARVVICDKDESGGRALEQEL-----PGAVFILCDVTQEDDVKTLVSE 75
Cdd:cd08933    1 MASGLRYADKVVIVTGGSRGIGRGIVRAFVENGAKVVFCARGEAAGQALESELnragpGSCKFVPCDVTKEEDIKTLISV 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530416654  76 TIRRFGRLDCVVNNAGHHPPPQRPEETSAQGFRQLLELNLLGTYTLTKLALPYLRKSQGNVINISSLVGAIGQAQAVPYV 155
Cdd:cd08933   81 TVERFGRIDCLVNNAGWHPPHQTTDETSAQEFRDLLNLNLISYFLASKYALPHLRKSQGNIINLSSLVGSIGQKQAAPYV 160

                        170       180
                 ....*....|....*....|....*.
gi 530416654 156 ATKGAVTAMTKALALDESPYGVRVNC 181
Cdd:cd08933  161 ATKGAITAMTKALAVDESRYGVRVNC 186

retinal dehydrogenase-like, classical (c) SDR; These classical SDRs includes members identified as retinol dehydrogenases, which convert retinol to retinal, a property that overlaps with 17betaHSD activity. 17beta-dehydrogenases are a group of isozymes that catalyze activation and inactivation of estrogen and androgens, and include members of the short-chain dehydrogenases/reductase 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 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 530416654   1 MATGTRYAGKVVVVTGGGRGIGAGIVRAFVNSGARVVICDKDESGGRALEQEL-----PGAVFILCDVTQEDDVKTLVSE 75
Cdd:cd08933    1 MASGLRYADKVVIVTGGSRGIGRGIVRAFVENGAKVVFCARGEAAGQALESELnragpGSCKFVPCDVTKEEDIKTLISV 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530416654  76 TIRRFGRLDCVVNNAGHHPPPQRPEETSAQGFRQLLELNLLGTYTLTKLALPYLRKSQGNVINISSLVGAIGQAQAVPYV 155
Cdd:cd08933   81 TVERFGRIDCLVNNAGWHPPHQTTDETSAQEFRDLLNLNLISYFLASKYALPHLRKSQGNIINLSSLVGSIGQKQAAPYV 160

                        170       180
                 ....*....|....*....|....*.
gi 530416654 156 ATKGAVTAMTKALALDESPYGVRVNC 181
Cdd:cd08933  161 ATKGAITAMTKALAVDESRYGVRVNC 186

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 530416654  18 GRGIGAGIVRAFVNSGARVVICDKDESGGRALEQELPG----AVFILCDVTQEDDVKTLVSETIRRFGRLDCVVNNAGhH 93
Cdd:COG1028   15 SSGIGRAIARALAAEGARVVITDRDAEALEAAAAELRAaggrALAVAADVTDEAAVEALVAAAVAAFGRLDILVNNAG-I 93

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530416654  94 PPPQRPEETSAQGFRQLLELNLLGTYTLTKLALPYLRKSQ-GNVINISSLVGAIGQAQAVPYVATKGAVTAMTKALALDE 172
Cdd:COG1028   94 TPPGPLEELTEEDWDRVLDVNLKGPFLLTRAALPHMRERGgGRIVNISSIAGLRGSPGQAAYAASKAAVVGLTRSLALEL 173

                 ....*....
gi 530416654 173 SPYGVRVNC 181
Cdd:COG1028  174 APRGIRVNA 182

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        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530416654   72 LVSETIRRFGRLDCVVNNA-GHHPPPQRP-EETSAQGFRQLLEL---NLLGTYTLTKLAL------------PYLRKSQG 134
Cdd:TIGR02685  74 IIDACFRAFGRCDVLVNNAsAFYPTPLLRgDAGEGVGDKKSLEVqvaELFGSNAIAPYFLikafaqrqagtrAEQRSTNL 153

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*.
gi 530416654  135 NVINISSLVGAIGQAQAVPYVATKGAVTAMTKALALDESPYGVRVN 180
Cdd:TIGR02685 154 SIVNLCDAMTDQPLLGFTMYTMAKHALEGLTRSAALELAPLQIRVN 199

retinal dehydrogenase-like, classical (c) SDR; These classical SDRs includes members identified as retinol dehydrogenases, which convert retinol to retinal, a property that overlaps with 17betaHSD activity. 17beta-dehydrogenases are a group of isozymes that catalyze activation and inactivation of estrogen and androgens, and include members of the short-chain dehydrogenases/reductase 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 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 530416654   1 MATGTRYAGKVVVVTGGGRGIGAGIVRAFVNSGARVVICDKDESGGRALEQEL-----PGAVFILCDVTQEDDVKTLVSE 75
Cdd:cd08933    1 MASGLRYADKVVIVTGGSRGIGRGIVRAFVENGAKVVFCARGEAAGQALESELnragpGSCKFVPCDVTKEEDIKTLISV 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530416654  76 TIRRFGRLDCVVNNAGHHPPPQRPEETSAQGFRQLLELNLLGTYTLTKLALPYLRKSQGNVINISSLVGAIGQAQAVPYV 155
Cdd:cd08933   81 TVERFGRIDCLVNNAGWHPPHQTTDETSAQEFRDLLNLNLISYFLASKYALPHLRKSQGNIINLSSLVGSIGQKQAAPYV 160

                        170       180
                 ....*....|....*....|....*.
gi 530416654 156 ATKGAVTAMTKALALDESPYGVRVNC 181
Cdd:cd08933  161 ATKGAITAMTKALAVDESRYGVRVNC 186

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530416654   26 VRAFVNSGARVVICDKDESGGRALEQELPG----AVFILCDVTQEDDVKTLVSETIRRFGRLDCVVNNAGHhPPPQRPEE 101
Cdd:pfam00106  17 AKRLAKEGAKVVLVDRSEEKLEAVAKELGAlggkALFIQGDVTDRAQVKALVEQAVERLGRLDILVNNAGI-TGLGPFSE 95

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530416654  102 TSAQGFRQLLELNLLGTYTLTKLALPYL-RKSQGNVINISSLVGAIGQAQAVPYVATKGAVTAMTKALALDESPYGVRVN 180
Cdd:pfam00106  96 LSDEDWERVIDVNLTGVFNLTRAVLPAMiKGSGGRIVNISSVAGLVPYPGGSAYSASKAAVIGFTRSLALELAPHGIRVN 175

                  .
gi 530416654  181 C 181
Cdd:pfam00106 176 A 176

3-oxoacyl-ACP reductase FabG;

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530416654  27 RAFVNSGARVVICDKDESGGRALEQELPG----AVFILCDVTQEDDVKTLVSETIRRFGRLDCVVNNAGHHPPPQRPEET 102
Cdd:PRK05653  23 LRLAADGAKVVIYDSNEEAAEALAAELRAaggeARVLVFDVSDEAAVRALIEAAVEAFGALDILVNNAGITRDALLPRMS 102

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530416654 103 SAQgFRQLLELNLLGTYTLTKLALPYLRKS-QGNVINISSLVGAIGQAQAVPYVATKGAVTAMTKALALDESPYGVRVNC 181
Cdd:PRK05653 103 EED-WDRVIDVNLTGTFNVVRAALPPMIKArYGRIVNISSVSGVTGNPGQTNYSAAKAGVIGFTKALALELASRGITVNA 181

NADP-dependent 3-hydroxy acid dehydrogenase YdfG [Energy production and conversion]; NADP-dependent 3-hydroxy acid dehydrogenase YdfG is part of the Pathway/BioSystem: Pyrimidine degradation

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530416654  18 GRGIGAGIVRAFVNSGARVVICDKDESGGRALEQELPGAVFIL-CDVTQEDDVKTLVSETIRRFGRLDCVVNNAGHHpPP 96
Cdd:COG4221   14 SSGIGAATARALAAAGARVVLAARRAERLEALAAELGGRALAVpLDVTDEAAVEAAVAAAVAEFGRLDVLVNNAGVA-LL 92

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530416654  97 QRPEETSAQGFRQLLELNLLGTYTLTKLALPYLRKSQ-GNVINISSLVGAIGQAQAVPYVATKGAVTAMTKALALDESPY 175
Cdd:COG4221   93 GPLEELDPEDWDRMIDVNVKGVLYVTRAALPAMRARGsGHIVNISSIAGLRPYPGGAVYAATKAAVRGLSESLRAELRPT 172

                 ....
gi 530416654 176 GVRV 179
Cdd:COG4221  173 GIRV 176

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530416654  26 VRAFVNSGARVVI-CDKDESGGRALEQELPG----AVFILCDVTQEDDVKTLVSETIRRFGRLDCVVNNAGHHPPpQRPE 100
Cdd:PRK12825  23 ALRLARAGADVVVhYRSDEEAAEELVEAVEAlgrrAQAVQADVTDKAALEAAVAAAVERFGRIDILVNNAGIFED-KPLA 101

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530416654 101 ETSAQGFRQLLELNLLGTYTLTKLALPYLRKSQ-GNVINISSLVGAIGQAQAVPYVATKGAVTAMTKALALDESPYGVRV 179
Cdd:PRK12825 102 DMSDDEWDEVIDVNLSGVFHLLRAVVPPMRKQRgGRIVNISSVAGLPGWPGRSNYAAAKAGLVGLTKALARELAEYGITV 181

                 ..
gi 530416654 180 NC 181
Cdd:PRK12825 182 NM 183

Short-chain dehydrogenase [General function prediction only];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530416654  18 GRGIGAGIVRAFVNSGARVVICDKDESGGRALEQELP----GAVFILCDVTQEDDVKTLVSETIRRFGRLDCVVNNAGHH 93
Cdd:COG0300   14 SSGIGRALARALAARGARVVLVARDAERLEALAAELRaagaRVEVVALDVTDPDAVAALAEAVLARFGPIDVLVNNAGVG 93

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530416654  94 pPPQRPEETSAQGFRQLLELNLLGTYTLTKLALPYLRKS-QGNVINISSLVGAIGQAQAVPYVATKGAVTAMTKALALDE 172
Cdd:COG0300   94 -GGGPFEELDLEDLRRVFEVNVFGPVRLTRALLPLMRARgRGRIVNVSSVAGLRGLPGMAAYAASKAALEGFSESLRAEL 172

                        170       180       190
                 ....*....|....*....|....*....|....*..
gi 530416654 173 SPYGVRVNC-HWAAWASPLRSGLRQCSWPPKPTSARA 208
Cdd:COG0300  173 APTGVRVTAvCPGPVDTPFTARAGAPAGRPLLSPEEV 209

Trans-2-enoyl-CoA reductase (TER) and 2,4-dienoyl-CoA reductase (DECR), atypical (a) SDR; TTER is a peroxisomal protein with a proposed role in fatty acid elongation. Fatty acid synthesis is known to occur in the both endoplasmic reticulum and mitochondria; peroxisomal TER has been proposed as an additional fatty acid elongation system, it reduces the double bond at C-2 as the last step of elongation. This system resembles the mitochondrial system in that acetyl-CoA is used as a carbon donor. TER may also function in phytol metabolism, reducting phytenoyl-CoA to phytanoyl-CoA in peroxisomes. DECR processes double bonds in fatty acids to increase their utility in fatty acid metabolism; it reduces 2,4-dienoyl-CoA to an enoyl-CoA. DECR is active in mitochondria and peroxisomes. This subgroup has the Gly-rich NAD-binding motif of the classical SDR family, but does not display strong identity to the canonical active site tetrad, and lacks the characteristic Tyr at the usual position. 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 530416654  27 RAFVNSGARVVIC----DKDESGGRALEQELPGAVFIL-CDVTQEDDVKTLVSETIRRFGRLDCVVNNA-GHHPPPQrpE 100
Cdd:cd05369   21 KAFAELGASVAIAgrkpEVLEAAAEEISSATGGRAHPIqCDVRDPEAVEAAVDETLKEFGKIDILINNAaGNFLAPA--E 98

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530416654 101 ETSAQGFRQLLELNLLGTYTLTKLALPYLRKSQ--GNVINISSLVGAIGQAQAVPYVATKGAVTAMTKALALDESPYGVR 178
Cdd:cd05369   99 SLSPNGFKTVIDIDLNGTFNTTKAVGKRLIEAKhgGSILNISATYAYTGSPFQVHSAAAKAGVDALTRSLAVEWGPYGIR 178

                 ...
gi 530416654 179 VNC 181
Cdd:cd05369  179 VNA 181

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 530416654  16 GGGRGIGAGIVRAFVNSGARVVICDKDESGGRALEQEL-PGAVFILCDVTQEDDVKTLVSETIRRFGRLDCVVNNAGhHP 94
Cdd:cd05341   12 GGARGLGLAHARLLVAEGAKVVLSDILDEEGQAAAAELgDAARFFHLDVTDEDGWTAVVDTAREAFGRLDVLVNNAG-IL 90

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530416654  95 PPQRPEETSAQGFRQLLELNLLGTYTLTKLALPYLRKS-QGNVINISSLVGAIGQAQAVPYVATKGAVTAMTKALALDES 173
Cdd:cd05341   91 TGGTVETTTLEEWRRLLDINLTGVFLGTRAVIPPMKEAgGGSIINMSSIEGLVGDPALAAYNASKGAVRGLTKSAALECA 170

                 ....*....
gi 530416654 174 P--YGVRVN 180
Cdd:cd05341  171 TqgYGIRVN 179

short chain dehydrogenase; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530416654  27 RAFVNSGARVVICDKDESGGRALEQELPGAVFI--LCDVTQEDDVKTLVSETIRRFGRLDCVVNNAGHHPPPQRPEETSA 104
Cdd:PRK12829  29 EAFAEAGARVHVCDVSEAALAATAARLPGAKVTatVADVADPAQVERVFDTAVERFGGLDVLVNNAGIAGPTGGIDEITP 108

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 530416654 105 QGFRQLLELNLLGTYTLTKLALPYLRKSQ--GNVINISSLVGAIGQAQAVPYVATKGAVTAMTKALALDESPYGVRVN 180
Cdd:PRK12829 109 EQWEQTLAVNLNGQFYFARAAVPLLKASGhgGVIIALSSVAGRLGYPGRTPYAASKWAVVGLVKSLAIELGPLGIRVN 186

putative beta-ketoacyl acyl carrier protein [ACP] reductase (BKR), subgroup 3, classical (c) SDR; This subgroup includes the putative Brucella melitensis biovar Abortus 2308 BKR, FabG, Mesorhizobium loti MAFF303099 FabG, and other classical SDRs. BKR, a member of the SDR family, catalyzes the NADPH-dependent reduction of acyl carrier protein in the first reductive step of de novo fatty acid synthesis (FAS). FAS consists of 4 elongation steps, which are repeated to extend the fatty acid chain thru the addition of two-carbo units from malonyl acyl-carrier protein (ACP): condensation, reduction, dehydration, and final reduction. Type II FAS, typical of plants and many bacteria, maintains these activities on discrete polypeptides, while type I Fas utilizes one or 2 multifunctional polypeptides. BKR resembles enoyl reductase, which catalyzes the second reduction step in FAS. SDRs are a functionally diverse family of oxidoreductases that have a single domain with a structurally conserved Rossmann fold (alpha/beta folding pattern with a central beta-sheet), an NAD(P)(H)-binding region, and a structurally diverse C-terminal region. Classical SDRs are typically about 250 residues long, while extended SDRS are approximately 350 residues. Sequence identity between different SDR enzymes are typically in the 15-30% range, but the enzymes share the Rossmann fold NAD-binding motif and characteristic NAD-binding and catalytic sequence patterns. These enzymes have a 3-glycine N-terminal NAD(P)(H)-binding pattern (typically, TGxxxGxG in classical SDRs and TGxxGxxG in extended SDRs), while substrate binding is in the C-terminal region. A critical catalytic Tyr residue (Tyr-151, human 15-hydroxyprostaglandin dehydrogenase (15-PGDH) numbering), is often found in a conserved YXXXK pattern. In addition to the Tyr and Lys, there is often an upstream Ser (Ser-138, 15-PGDH numbering) and/or an Asn (Asn-107, 15-PGDH numbering) or additional Ser, contributing to the active site. Substrates for these enzymes include sugars, steroids, alcohols, and aromatic compounds. The standard reaction mechanism is a proton relay involving the conserved Tyr and Lys, as well as Asn (or Ser). Some SDR family members, including 17 beta-hydroxysteroid dehydrogenase contain an additional helix-turn-helix motif that is not generally found among SDRs.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530416654  26 VRAFVNSGARVVICDKDESGGRALEQELP-GAVFILCDVTQEDDVKTLVSETIRRFGRLDCVVNNAG--HHPPPQrpEET 102
Cdd:cd05345   22 ARRFAQEGARVVIADINADGAERVAADIGeAAIAIQADVTKRADVEAMVEAALSKFGRLDILVNNAGitHRNKPM--LEV 99

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530416654 103 SAQGFRQLLELNLLGTYTLTKLALPYLRKSQGNVI-NISSLVGAIGQAQAVPYVATKGAVTAMTKALALDESPYGVRVNC 181
Cdd:cd05345  100 DEEEFDRVFAVNVKSIYLSAQALVPHMEEQGGGVIiNIASTAGLRPRPGLTWYNASKGWVVTATKAMAVELAPRNIRVNC 179

17hydroxysteroid dehydrogenase type 10 (HSD10)-like, classical (c) SDRs; HSD10, also known as amyloid-peptide-binding alcohol dehydrogenase (ABAD), was previously identified as a L-3-hydroxyacyl-CoA dehydrogenase, HADH2. In fatty acid metabolism, HADH2 catalyzes the third step of beta-oxidation, the conversion of a hydroxyl to a keto group in the NAD-dependent oxidation of L-3-hydroxyacyl CoA. In addition to alcohol dehydrogenase and HADH2 activites, HSD10 has steroid dehydrogenase activity. Although the mechanism is unclear, HSD10 is implicated in the formation of amyloid beta-petide in the brain (which is linked to the development of Alzheimer's disease). Although HSD10 is normally concentrated in the mitochondria, in the presence of amyloid beta-peptide it translocates into the plasma membrane, where it's action may generate cytotoxic aldehydes and may lower estrogen levels through its use of 17-beta-estradiol as a substrate. HSD10 is a member of the SRD family, but differs from other SDRs by the presence of two insertions of unknown function. 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 530416654  26 VRAFVNSGARVVICDKDESGGRALEQELPGAVFILCDVTQEDDVKTLVSETIRRFGRLDCVVNNAG-------------- 91
Cdd:cd05371   19 VERLLAQGAKVVILDLPNSPGETVAKLGDNCRFVPVDVTSEKDVKAALALAKAKFGRLDIVVNCAGiavaaktynkkgqq 98

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530416654  92 HHPPPQrpeetsaqgFRQLLELNLLGTYTLTKLALPYLRKSQGN-------VINISSLVGAIGQAQAVPYVATKGAVTAM 164
Cdd:cd05371   99 PHSLEL---------FQRVINVNLIGTFNVIRLAAGAMGKNEPDqggergvIINTASVAAFEGQIGQAAYSASKGGIVGM 169

                        170
                 ....*....|....*.
gi 530416654 165 TKALALDESPYGVRVN 180
Cdd:cd05371  170 TLPIARDLAPQGIRVV 185

short chain dehydrogenase; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530416654  27 RAFVNSGARVVICDKDESGGRALEQELPG----AVFILCDVTQEDDVKTLVSETIRRFGRLDCVVNNAGHHPPPQRPEET 102
Cdd:PRK07890  23 VRAARAGADVVLAARTAERLDEVAAEIDDlgrrALAVPTDITDEDQCANLVALALERFGRVDALVNNAFRVPSMKPLADA 102

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 530416654 103 SAQGFRQLLELNLLGTYTLTKLALPYLRKSQGNVINISSLVGAIGQAQAVPYVATKGAVTAMTKALALDESPYGVRVN 180
Cdd:PRK07890 103 DFAHWRAVIELNVLGTLRLTQAFTPALAESGGSIVMINSMVLRHSQPKYGAYKMAKGALLAASQSLATELGPQGIRVN 180

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 530416654  27 RAFVNSGARVVICD----KDESGGRALEQELPGAVFILCDVTQEDDVKTLVSETIRRFGRLDCVVNNAG-HHPPPQrpEE 101
Cdd:cd05347   23 SGLAEAGANIVINSrneeKAEEAQQLIEKEGVEATAFTCDVSDEEAIKAAVEAIEEDFGKIDILVNNAGiIRRHPA--EE 100

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530416654 102 TSAQGFRQLLELNLLGTYTLTKLALPYLRKS-QGNVINISSLVGAIGQAQAVPYVATKGAVTAMTKALALDESPYGVRVN 180
Cdd:cd05347  101 FPEAEWRDVIDVNLNGVFFVSQAVARHMIKQgHGKIINICSLLSELGGPPVPAYAASKGGVAGLTKALATEWARHGIQVN 180

short chain dehydrogenase; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530416654  28 AFVNSGARVVICDKDESGG-----RALEQELPGAVFILCDVTQEDDVKTLVSETIRRFGRLDCVVNNAGHHPPPQRPEET 102
Cdd:PRK06701  65 LFAKEGADIAIVYLDEHEDanetkQRVEKEGVKCLLIPGDVSDEAFCKDAVEETVRELGRLDILVNNAAFQYPQQSLEDI 144

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 530416654 103 SAQGFRQLLELNLLGTYTLTKLALPYLrKSQGNVINISSLVGAIGQAQAVPYVATKGAVTAMTKALALDESPYGVRVNC 181
Cdd:PRK06701 145 TAEQLDKTFKTNIYSYFHMTKAALPHL-KQGSAIINTGSITGYEGNETLIDYSATKGAIHAFTRSLAQSLVQKGIRVNA 222

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 530416654  26 VRAFVNSGARVVI-CDKDESGGRALEQELPG----AVFILCDVTQEDDVKTLVSETIRRFGRLDCVVNNAGHhpppQRPE 100
Cdd:cd05358   20 AIRLATAGANVVVnYRSKEDAAEEVVEEIKAvggkAIAVQADVSKEEDVVALFQSAIKEFGTLDILVNNAGL----QGDA 95

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530416654 101 ---ETSAQGFRQLLELNLLGTYTLTKLALPYLRKSQ--GNVINISSLVGAIGQAQAVPYVATKGAVTAMTKALALDESPY 175
Cdd:cd05358   96 sshEMTLEDWNKVIDVNLTGQFLCAREAIKRFRKSKikGKIINMSSVHEKIPWPGHVNYAASKGGVKMMTKTLAQEYAPK 175

                 ....*.
gi 530416654 176 GVRVNC 181
Cdd:cd05358  176 GIRVNA 181

short chain dehydrogenase; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530416654  18 GRGIGAGIVRAFVNSGARVVICDKDESGGRALEQELpGAVFILCDVTQEDDVKTLVSETIRRFGRLDCVVNNAGHHPPPQ 97
Cdd:PRK06057  16 GSGIGLATARRLAAEGATVVVGDIDPEAGKAAADEV-GGLFVPTDVTDEDAVNALFDTAAETYGSVDIAFNNAGISPPED 94

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530416654  98 RP-EETSAQGFRQLLELNLLGTYTLTKLALPYLRKSQ-GNVINISSLVGAIGQAQA-VPYVATKGAVTAMTKALALDESP 174
Cdd:PRK06057  95 DSiLNTGLDAWQRVQDVNLTSVYLCCKAALPHMVRQGkGSIINTASFVAVMGSATSqISYTASKGGVLAMSRELGVQFAR 174

                 ....*.
gi 530416654 175 YGVRVN 180
Cdd:PRK06057 175 QGIRVN 180

3-hydroxybutyrate dehydrogenase; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530416654  18 GRGIGAGIVRAFVNSGARVVICDKDESGGRALEQELPG----AVFILCDVTQEDDVKTLVSETIRRFGRLDCVVNNAG-H 92
Cdd:PRK12429  13 ASGIGLEIALALAKEGAKVVIADLNDEAAAAAAEALQKaggkAIGVAMDVTDEEAINAGIDYAVETFGGVDILVNNAGiQ 92

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530416654  93 HPPPQrpEETSAQGFRQLLELNLLGTYTLTKLALPYLRKSQ-GNVINISSLVGAIGQAQAVPYVATKGAVTAMTKALALD 171
Cdd:PRK12429  93 HVAPI--EDFPTEKWKKMIAIMLDGAFLTTKAALPIMKAQGgGRIINMASVHGLVGSAGKAAYVSAKHGLIGLTKVVALE 170

                        170
                 ....*....|
gi 530416654 172 ESPYGVRVNC 181
Cdd:PRK12429 171 GATHGVTVNA 180