short chain dehydrogenase; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958668140  36 LPLQADRVAIVTGATRGVGLSTACQLARLGMRVIVAGNDEHRGHEVVARIQEESGPESAHFLFLDLASLSSVRSFVRNFE 115
Cdd:PRK06197   11 IPDQSGRVAVVTGANTGLGYETAAALAAKGAHVVLAVRNLDKGKAAAARITAATPGADVTLQELDLTSLASVRAAADALR 90

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1958668140 116 ATALPLHLLINNAGVMLDPSGNTKDGFERHVGVNFLGHFLLTSLLLPALRASghqgRKSRVITVCSSTH 184
Cdd:PRK06197   91 AAYPRIDLLINNAGVMYTPKQTTADGFELQFGTNHLGHFALTGLLLDRLLPV----PGSRVVTVSSGGH 155

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958668140  42 RVAIVTGATRGVGLSTACQLARLGMRVIVAGNDEHRGHEVVARIQEESGpeSAHFLFLDLASLSSVRSFVRNFEATALPL 121
Cdd:pfam00106   1 KVALVTGASSGIGRAIAKRLAKEGAKVVLVDRSEEKLEAVAKELGALGG--KALFIQGDVTDRAQVKALVEQAVERLGRL 78

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1958668140 122 HLLINNAGVMLD-PSGNTKDG-FERHVGVNFLGHFLLTSLLLPALrASGHQGrksRVITVCS 181
Cdd:pfam00106  79 DILVNNAGITGLgPFSELSDEdWERVIDVNLTGVFNLTRAVLPAM-IKGSGG---RIVNISS 136

retinol dehydrogenases (retinol-DHs), classical (c) SDRs; Classical SDR-like subgroup containing retinol-DHs and related proteins. Retinol is processed by a medium chain alcohol dehydrogenase followed by retinol-DHs. Proteins in this subfamily share the glycine-rich NAD-binding motif of the classical SDRs, have a partial match to the canonical active site tetrad, but lack the typical active site Ser. This subgroup includes the human proteins: retinol dehydrogenase -12, -13 ,and -14. 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 1958668140  42 RVAIVTGATRGVGLSTACQLARLGMRVIVAGNDEHRGHEVVARIQEESGPESAHFLFLDLASLSSVRSFVRNFEATALPL 121
Cdd:cd09807     2 KTVIITGANTGIGKETARELARRGARVIMACRDMAKCEEAAAEIRRDTLNHEVIVRHLDLASLKSIRAFAAEFLAEEDRL 81

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1958668140 122 HLLINNAGVMLDPSGNTKDGFERHVGVNFLGHFLLTSLLLPALRASGhqgrKSRVITVCSSTHWVGQADVARLLGQRP 199
Cdd:cd09807    82 DVLINNAGVMRCPYSKTEDGFEMQFGVNHLGHFLLTNLLLDLLKKSA----PSRIVNVSSLAHKAGKINFDDLNSEKS 155

human WWOX (WW domain-containing oxidoreductase)-like, classical (c)-like SDRs; Classical-like SDR domain of human WWOX and related proteins. Proteins in this subfamily share the glycine-rich NAD-binding motif of the classical SDRs, have a partial match to the canonical active site tetrad, but lack the typical active site 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 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 1958668140  41 DRVAIVTGATRGVGLSTACQLARLGMRVIVAGNDEHRGHEVVARIQEESGPESAHFLFLDLASLSSVRSFVRNFEATALP 120
Cdd:cd09809     1 GKVIIITGANSGIGFETARSFALHGAHVILACRNMSRASAAVSRILEEWHKARVEAMTLDLASLRSVQRFAEAFKAKNSP 80

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1958668140 121 LHLLINNAGVMLDPSGNTKDGFERHVGVNFLGHFLLTSLLLPALRASGhqgrKSRVITVCSSTH 184
Cdd:cd09809    81 LHVLVCNAAVFALPWTLTEDGLETTFQVNHLGHFYLVQLLEDVLRRSA----PARVIVVSSESH 140

oxidoreductase; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958668140  42 RVAIVTGATRGVGLSTACQLARLGMRVIVAGNDEHRGHEVVARIQEESgpesahFLFLDLASLSSVRSFVRNFEATALPL 121
Cdd:PRK06196   27 KTAIVTGGYSGLGLETTRALAQAGAHVIVPARRPDVAREALAGIDGVE------VVMLDLADLESVRAFAERFLDSGRRI 100

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1958668140 122 HLLINNAGVMLDPSGNTKDGFERHVGVNFLGHFLLTSLLLPALRAsghqGRKSRVITVCSSTH 184
Cdd:PRK06196  101 DILINNAGVMACPETRVGDGWEAQFATNHLGHFALVNLLWPALAA----GAGARVVALSSAGH 159

protochlorophyllide reductase

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958668140  45 IVTGATRGVGLSTACQLARLG-MRVIVAGNDEHRGhEVVARiqeESG--PESAHFLFLDLASLSSVRSFVRNFEATALPL 121
Cdd:PLN00015    1 IITGASSGLGLATAKALAETGkWHVVMACRDFLKA-ERAAK---SAGmpKDSYTVMHLDLASLDSVRQFVDNFRRSGRPL 76

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958668140 122 HLLINNAGVMLdPSGN----TKDGFERHVGVNFLGHFLLTSLLLPALRASGHQGRksRVITVCSSThwvgqADVARLLGQ 197
Cdd:PLN00015   77 DVLVCNAAVYL-PTAKeptfTADGFELSVGTNHLGHFLLSRLLLDDLKKSDYPSK--RLIIVGSIT-----GNTNTLAGN 148

                  ....*...
gi 1958668140 198 RPPMRGLG 205
Cdd:PLN00015  149 VPPKANLG 156

Light-dependent NADPH-protochlorophyllide oxidoreductase [Coenzyme transport and metabolism];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958668140  39 QADRVAIVTGATRGVGLSTACQLARLGMRVIVAGNDEHRGHEVVARIQEESGPESAhfLFLDLASLSSVRSFVRNFEATA 118
Cdd:COG5748     4 DQKSTVIITGASSGVGLYAAKALADRGWHVIMACRDLEKAEAAAQELGIPPDSYTI--IHIDLASLESVRRFVADFRALG 81

                          90       100       110
                  ....*....|....*....|....*....|....*....
gi 1958668140 119 LPLHLLINNAGV---MLDPSGNTKDGFERHVGVNFLGHF 154
Cdd:COG5748    82 RPLDALVCNAAVyypLLKEPLRSPDGYELSVATNHLGHF 120

Porcine testicular carbonyl reductase (PTCR)-like, classical (c) SDRs; PTCR is a classical SDR which catalyzes the NADPH-dependent reduction of ketones on steroids and prostaglandins. Unlike most SDRs, PTCR functions as a monomer. This subgroup also includes human carbonyl reductase 1 (CBR1) and CBR3. CBR1 is an NADPH-dependent SDR with broad substrate specificity and may be responsible for the in vivo reduction of quinones, prostaglandins, and other carbonyl-containing compounds. In addition it includes poppy NADPH-dependent salutaridine reductase which catalyzes the stereospecific reduction of salutaridine to 7(S)-salutaridinol in the biosynthesis of morphine, and Arabidopsis SDR1,a menthone reductase, which catalyzes the reduction of menthone to neomenthol, a compound with antimicrobial activity; SDR1 can also carry out neomenthol oxidation. 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, 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 1958668140  42 RVAIVTGATRGVGLSTACQLARLGM-RVIVAGNDEHRGHEVVARIQEESgpESAHFLFLDLASLSSVRSFVRNFEATALP 120
Cdd:cd05324     1 KVALVTGANRGIGFEIVRQLAKSGPgTVILTARDVERGQAAVEKLRAEG--LSVRFHQLDVTDDASIEAAADFVEEKYGG 78

                          90       100       110
                  ....*....|....*....|....*....|....*
gi 1958668140 121 LHLLINNAGVML---DPSGNTKDGFERHVGVNFLG 152
Cdd:cd05324    79 LDILVNNAGIAFkgfDDSTPTREQARETMKTNFFG 113

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958668140  44 AIVTGATRGVGLSTACQLARLGMRVIVAGNDEHRGHEVVAriqEESGPESAHFLFLDLASLSSVRSFVRNFEATALPLHL 123
Cdd:cd05233     1 ALVTGASSGIGRAIARRLAREGAKVVLADRNEEALAELAA---IEALGGNAVAVQADVSDEEDVEALVEEALEEFGRLDI 77

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958668140 124 LINNAGVMLDPSGN--TKDGFERHVGVNFLGHFLLTSLLLPALRAsghqGRKSRVITVCS 181
Cdd:cd05233    78 LVNNAGIARPGPLEelTDEDWDRVLDVNLTGVFLLTRAALPHMKK----QGGGRIVNISS 133

human dehydrogenase/reductase SDR family member (DHRS)-12/FLJ13639-like, classical (c)-like SDRs; Classical SDR-like subgroup containing human DHRS-12/FLJ13639, the 36K protein of zebrafish CNS myelin, and related proteins. DHRS-12/FLJ13639 is expressed in neurons and oligodendrocytes in the human cerebral cortex. Proteins in this subgroup share the glycine-rich NAD-binding motif of the classical SDRs, have a partial match to the canonical active site tetrad, but lack the typical active site 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 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 1958668140  42 RVAIVTGATRGVGLSTACQLARLGMRVIVAGNDEHRGHEVVARIQEESGPESAHFLFLDLASLSSVRSFVRNFEATALPL 121
Cdd:cd09808     2 RSFLITGANSGIGKAAALAIAKRGGTVHMVCRNQTRAEEARKEIETESGNQNIFLHIVDMSDPKQVWEFVEEFKEEGKKL 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958668140 122 HLLINNAGVMLDPSGNTKDGFERHVGVNFLGHFLLTSLLLPALRASghqgRKSRVITVCSSTHWVGQADVARLLGQRPPM 201
Cdd:cd09808    82 HVLINNAGCMVNKRELTEDGLEKNFATNTLGTYILTTHLIPVLEKE----EDPRVITVSSGGMLVQKLNTNNLQSERTAF 157

                  ..
gi 1958668140 202 RG 203
Cdd:cd09808   158 DG 159

short chain dehydrogenase; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958668140  38 LQADRVAIVTGATRGVGLSTACQLARLGMRVIVAGNDEHRGHEVVARIQEESGpeSAHFLFLDLASLSSVRSFVRNFEAT 117
Cdd:PRK12939    4 NLAGKRALVTGAARGLGAAFAEALAEAGATVAFNDGLAAEARELAAALEAAGG--RAHAIAADLADPASVQRFFDAAAAA 81

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958668140 118 ALPLHLLINNAGVMldPSGN----TKDGFERHVGVNFLGHFLLTSLLLPALRASGHqgrkSRVITVCSST 183
Cdd:PRK12939   82 LGGLDGLVNNAGIT--NSKSatelDIDTWDAVMNVNVRGTFLMLRAALPHLRDSGR----GRIVNLASDT 145

tetrahydroxynaphthalene/trihydroxynaphthalene reductase-like, classical (c) SDRs; 1,3,6,8-tetrahydroxynaphthalene reductase (4HNR) of Magnaporthe grisea and the related 1,3,8-trihydroxynaphthalene reductase (3HNR) are typical members of the SDR family containing the canonical glycine rich NAD(P)-binding site and active site tetrad, and function in fungal melanin biosynthesis. This subgroup also includes an SDR from Norway spruce that may function to protect against both biotic and abitoic stress. 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 1958668140  42 RVAIVTGATRGVGLSTACQLARLGMRVIVA-GNDEHRGHEVVARIQEESGpeSAHFLFLDLASLSSVRSFVRNFEATALP 120
Cdd:cd05362     4 KVALVTGASRGIGRAIAKRLARDGASVVVNyASSKAAAEEVVAEIEAAGG--KAIAVQADVSDPSQVARLFDAAEKAFGG 81

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1958668140 121 LHLLINNAGVM-LDPSGNTKDG-FERHVGVNFLGHFlltsllLPALRASGHQGRKSRVITVCSST 183
Cdd:cd05362    82 VDILVNNAGVMlKKPIAETSEEeFDRMFTVNTKGAF------FVLQEAAKRLRDGGRIINISSSL 140

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958668140  42 RVAIVTGATRGVGLSTACQLARLGMRVIVAG-NDEHRGHEVVARIQEESGPesAHFLFLDLASLSSVRSFVRNFEATALP 120
Cdd:PRK12745    3 PVALVTGGRRGIGLGIARALAAAGFDLAINDrPDDEELAATQQELRALGVE--VIFFPADVADLSAHEAMLDAAQAAWGR 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|.
gi 1958668140 121 LHLLINNAGV-------MLDPsgnTKDGFERHVGVNFLGHF 154
Cdd:PRK12745   81 IDCLVNNAGVgvkvrgdLLDL---TPESFDRVLAINLRGPF 118

secoisolariciresinol dehydrogenase (secoisolariciresinol-DH)-like, classical (c) SDRs; Podophyllum secoisolariciresinol-DH is a homo tetrameric, classical SDR that catalyzes the NAD-dependent conversion of (-)-secoisolariciresinol to (-)-matairesinol via a (-)-lactol intermediate. (-)-Matairesinol is an intermediate to various 8'-lignans, including the cancer-preventive mammalian lignan, and those involved in vascular plant defense. This subgroup also includes rice momilactone A synthase which catalyzes the conversion of 3beta-hydroxy-9betaH-pimara-7,15-dien-19,6beta-olide into momilactone A, Arabidopsis ABA2 which during abscisic acid (ABA) biosynthesis, catalyzes the conversion of xanthoxin to abscisic aldehyde and, maize Tasselseed2 which participate in the maize sex determination pathway. 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, 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 1958668140  41 DRVAIVTGATRGVGLSTACQLARLGMRVIVAGNDEHRGHEVVARIqeesGPESAHFLFLDLaslsSVRSFVRNFEATALP 120
Cdd:cd05326     4 GKVAIITGGASGIGEATARLFAKHGARVVIADIDDDAGQAVAAEL----GDPDISFVHCDV----TVEADVRAAVDTAVA 75

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|..
gi 1958668140 121 LH----LLINNAGVMLDPSGN----TKDGFERHVGVNFLGHF 154
Cdd:cd05326    76 RFgrldIMFNNAGVLGAPCYSiletSLEEFERVLDVNVYGAF 117

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958668140  41 DRVAIVTGATRGVGLSTACQLARLGMRVIVAGNDEHRGHEVVARIQEESGPEsAHFLFLDLASLSSVRSFVRNFEATALP 120
Cdd:PRK05557    5 GKVALVTGASRGIGRAIAERLAAQGANVVINYASSEAGAEALVAEIGALGGK-ALAVQGDVSDAESVERAVDEAKAEFGG 83

                          90
                  ....*....|...
gi 1958668140 121 LHLLINNAGVMLD 133
Cdd:PRK05557   84 VDILVNNAGITRD 96

putative beta-ketoacyl acyl carrier protein [ACP] reductase (BKR), subgroup 1, classical (c) SDR; This subgroup includes Escherichia coli CFT073 FabG. The Escherichai coli K12 BKR, FabG, belongs to a different subgroup. 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 1958668140  42 RVAIVTGATRGVGLSTACQLARLGMRV-IVAGNDEHRGHEVVARIQEESGpeSAHFLFLDLASLSSVRSFVRNFEATALP 120
Cdd:cd05337     2 PVAIVTGASRGIGRAIATELAARGFDIaINDLPDDDQATEVVAEVLAAGR--RAIYFQADIGELSDHEALLDQAWEDFGR 79

                          90       100       110
                  ....*....|....*....|....*....|....*...
gi 1958668140 121 LHLLINNAGVMLDPSGN----TKDGFERHVGVNFLGHF 154
Cdd:cd05337    80 LDCLVNNAGIAVRPRGDlldlTEDSFDRLIAINLRGPF 117

SDR family oxidoreductase;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958668140  40 ADRVAIVTGATRGVGLSTACQLARLGMRVIVAGNDEHRGHEVVARIQEESGpeSAHFLFLDLASLSSVRSFVRNFEATAL 119
Cdd:PRK06172    6 SGKVALVTGGAAGIGRATALAFAREGAKVVVADRDAAGGEETVALIREAGG--EALFVACDVTRDAEVKALVEQTIAAYG 83

                          90       100       110
                  ....*....|....*....|....*....|....*.
gi 1958668140 120 PLHLLINNAGVMLDPSG---NTKDGFERHVGVNFLG 152
Cdd:PRK06172   84 RLDYAFNNAGIEIEQGRlaeGSEAEFDAIMGVNVKG 119

SDR family oxidoreductase;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958668140  40 ADRVAIVTGATRGVGLSTACQLARLGMRVIVAGNDEHRGHEVVARIQeesGPESAHFLFLDLASLSSVRSFVrnfeATAL 119
Cdd:PRK07231    4 EGKVAIVTGASSGIGEGIARRFAAEGARVVVTDRNEEAAERVAAEIL---AGGRAIAVAADVSDEADVEAAV----AAAL 76

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|...
gi 1958668140 120 P----LHLLINNAGV------MLDPsgnTKDGFERHVGVNFLG 152
Cdd:PRK07231   77 ErfgsVDILVNNAGTthrngpLLDV---DEAEFDRIFAVNVKS 116

SDR family oxidoreductase;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958668140  40 ADRVAIVTGATRGVGLSTACQLARLGMRVIVAGNDEHRGHEVVARIQEESGPESAHFLFLDLASLSSVRSFVRNFEATAL 119
Cdd:PRK07063    6 AGKVALVTGAAQGIGAAIARAFAREGAAVALADLDAALAERAAAAIARDVAGARVLAVPADVTDAASVAAAVAAAEEAFG 85

                          90       100       110
                  ....*....|....*....|....*....|....*
gi 1958668140 120 PLHLLINNAG--VMLDPSGNTKDGFERHVGVNFLG 152
Cdd:PRK07063   86 PLDVLVNNAGinVFADPLAMTDEDWRRCFAVDLDG 120

SDR family oxidoreductase;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958668140  42 RVAIVTGATRGVGLSTACQLARLGMRVIVAGNDEHRGHEVVARIQEESGpeSAHFLFLDLASLSSVRSFVRNFEATALPL 121
Cdd:PRK06949   10 KVALVTGASSGLGARFAQVLAQAGAKVVLASRRVERLKELRAEIEAEGG--AAHVVSLDVTDYQSIKAAVAHAETEAGTI 87

                  ....*....
gi 1958668140 122 HLLINNAGV 130
Cdd:PRK06949   88 DILVNNSGV 96

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958668140  42 RVAIVTGATRGVGLSTACQLARLGMRVIV-AGNDEHRGHEVVARIQEESGpeSAHFLFLDLASLSSVRSFVRNFEATALP 120
Cdd:PRK12825    7 RVALVTGAARGLGRAIALRLARAGADVVVhYRSDEEAAEELVEAVEALGR--RAQAVQADVTDKAALEAAVAAAVERFGR 84

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1958668140 121 LHLLINNAGVMLDPS--GNTKDGFERHVGVNFLGHFLLTSLLLPALRASghqgRKSRVITVCSST---HWVGQADVA 192
Cdd:PRK12825   85 IDILVNNAGIFEDKPlaDMSDDEWDEVIDVNLSGVFHLLRAVVPPMRKQ----RGGRIVNISSVAglpGWPGRSNYA 157

SDR family oxidoreductase;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958668140  42 RVAIVTGATRGVGLSTACQLARLGMRVIVAGNDEHRGHEVVARIQEESGPESAHFLFLDLASLSSVRSFvRNFEATALPL 121
Cdd:PRK06914    4 KIAIVTGASSGFGLLTTLELAKKGYLVIATMRNPEKQENLLSQATQLNLQQNIKVQQLDVTDQNSIHNF-QLVLKEIGRI 82

                          90       100       110
                  ....*....|....*....|....*....|....*.
gi 1958668140 122 HLLINNAGVMLdpSGNTKD----GFERHVGVNFLGH 153
Cdd:PRK06914   83 DLLVNNAGYAN--GGFVEEipveEYRKQFETNVFGA 116

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.