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 148670696  38 GKVAIVTGANTGIGKETAKDLAQRGARVYLACRDVDKGELAAREIQAVTGNSQVFVRKLDLADTKSIRAFAKDFLAEEKH 117
Cdd:cd09807    1 GKTVIITGANTGIGKETARELARRGARVIMACRDMAKCEEAAAEIRRDTLNHEVIVRHLDLASLKSIRAFAAEFLAEEDR 80

                         90       100       110
                 ....*....|....*....|....*....|.
gi 148670696 118 LHLLINNAGVMMCPYSKTADGFEMHIGVNHL 148
Cdd:cd09807   81 LDVLINNAGVMRCPYSKTEDGFEMQFGVNHL 111

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 148670696  38 GKVAIVTGANTGIGKETAKDLAQRGARVYLACRDVDKGELAAREIQAVTGNSQVFVRKLDLADTKSIRAFAKDFLAEEKH 117
Cdd:cd09807    1 GKTVIITGANTGIGKETARELARRGARVIMACRDMAKCEEAAAEIRRDTLNHEVIVRHLDLASLKSIRAFAAEFLAEEDR 80

                         90       100       110
                 ....*....|....*....|....*....|.
gi 148670696 118 LHLLINNAGVMMCPYSKTADGFEMHIGVNHL 148
Cdd:cd09807   81 LDVLINNAGVMRCPYSKTEDGFEMQFGVNHL 111

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 148670696  36 LPGKVAIVTGANTGIGKETAKDLAQRGARVYLACRDVDKGELAAREIQAVTGnsQVFVRKLDLADTKSIRAFAKDFLAEE 115
Cdd:COG1028    4 LKGKVALVTGGSSGIGRAIARALAAEGARVVITDRDAEALEAAAAELRAAGG--RALAVAADVTDEAAVEALVAAAVAAF 81

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|.
gi 148670696 116 KHLHLLINNAGVMM-CPYSK-TADGFEMHIGVNHLAIWAGS 154
Cdd:COG1028   82 GRLDILVNNAGITPpGPLEElTEEDWDRVLDVNLKGPFLLT 122

sepiapterin reductase; This model describes sepiapterin reductase, a member of the short chain dehydrogenase/reductase family. The enzyme catalyzes the last step in the biosynthesis of tetrahydrobiopterin. A similar enzyme in Bacillus cereus was isolated for its ability to convert benzil to (S)-benzoin, a property sepiapterin reductase also shares. Cutoff scores for this model are set such that benzil reductase scores between trusted and noise cutoffs.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148670696   40 VAIVTGANTGIGKETAKDLAQR----GARVYLACRDVDKGELAAREIQAVTGNSQVFVRKLDLADTKSIRAFAKDFLA-- 113
Cdd:TIGR01500   2 VCLVTGASRGFGRTIAQELAKClkspGSVLVLSARNDEALRQLKAEIGAERSGLRVVRVSLDLGAEAGLEQLLKALRElp 81

                          90
                  ....*....|....*..
gi 148670696  114 --EEKHLHLLINNAGVM 128
Cdd:TIGR01500  82 rpKGLQRLLLINNAGTL 98

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 148670696  38 GKVAIVTGANTGIGKETAKDLAQRGARVYLACRDVDKGELAAREIQAVTGNSQVFVRKLDLADTKSIRAFAKDFLAEEKH 117
Cdd:cd09807    1 GKTVIITGANTGIGKETARELARRGARVIMACRDMAKCEEAAAEIRRDTLNHEVIVRHLDLASLKSIRAFAAEFLAEEDR 80

                         90       100       110
                 ....*....|....*....|....*....|.
gi 148670696 118 LHLLINNAGVMMCPYSKTADGFEMHIGVNHL 148
Cdd:cd09807   81 LDVLINNAGVMRCPYSKTEDGFEMQFGVNHL 111

short chain dehydrogenase; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148670696  38 GKVAIVTGANTGIGKETAKDLAQRGARVYLACRDVDKGELAAREIQAVTGNSQVFVRKLDLADTKSIRAFAKDFLAEEKH 117
Cdd:PRK06197  16 GRVAVVTGANTGLGYETAAALAAKGAHVVLAVRNLDKGKAAAARITAATPGADVTLQELDLTSLASVRAAADALRAAYPR 95

                         90       100       110
                 ....*....|....*....|....*....|.
gi 148670696 118 LHLLINNAGVMMCPYSKTADGFEMHIGVNHL 148
Cdd:PRK06197  96 IDLLINNAGVMYTPKQTTADGFELQFGTNHL 126

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 148670696  38 GKVAIVTGANTGIGKETAKDLAQRGARVYLACRDVDKGELAAREIQAVTGNSQVFVRKLDLADTKSIRAFAKDFLAEEKH 117
Cdd:cd09808    1 GRSFLITGANSGIGKAAALAIAKRGGTVHMVCRNQTRAEEARKEIETESGNQNIFLHIVDMSDPKQVWEFVEEFKEEGKK 80

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|
gi 148670696 118 LHLLINNAGVMMCPYSKTADGFEMHIGVNHLAIWAGSTSI 157
Cdd:cd09808   81 LHVLINNAGCMVNKRELTEDGLEKNFATNTLGTYILTTHL 120

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 148670696  38 GKVAIVTGANTGIGKETAKDLAQRGARVYLACRDVDKGELAAREIQAVTGNSQVFVRKLDLADTKSIRAFAKDFLAEEKH 117
Cdd:cd09809    1 GKVIIITGANSGIGFETARSFALHGAHVILACRNMSRASAAVSRILEEWHKARVEAMTLDLASLRSVQRFAEAFKAKNSP 80

                         90       100       110
                 ....*....|....*....|....*....|..
gi 148670696 118 LHLLINNAGVMMCPYSKTADGFEMHIGVNHLA 149
Cdd:cd09809   81 LHVLVCNAAVFALPWTLTEDGLETTFQVNHLG 112

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 148670696  36 LPGKVAIVTGANTGIGKETAKDLAQRGARVYLACRDVDKGELAAREIQAVTGnsQVFVRKLDLADTKSIRAFAKDFLAEE 115
Cdd:COG1028    4 LKGKVALVTGGSSGIGRAIARALAAEGARVVITDRDAEALEAAAAELRAAGG--RALAVAADVTDEAAVEALVAAAVAAF 81

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|.
gi 148670696 116 KHLHLLINNAGVMM-CPYSK-TADGFEMHIGVNHLAIWAGS 154
Cdd:COG1028   82 GRLDILVNNAGITPpGPLEElTEEDWDRVLDVNLKGPFLLT 122

Short-chain dehydrogenase [General function prediction only];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148670696  35 QLPGKVAIVTGANTGIGKETAKDLAQRGARVYLACRDVDKGELAAREIQAVTGNsqVFVRKLDLADTKSIRAFAKDFLAE 114
Cdd:COG0300    2 SLTGKTVLITGASSGIGRALARALAARGARVVLVARDAERLEALAAELRAAGAR--VEVVALDVTDPDAVAALAEAVLAR 79

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....
gi 148670696 115 EKHLHLLINNAGVMmcPYSK----TADGFEMHIGVNHLAIWAGS 154
Cdd:COG0300   80 FGPIDVLVNNAGVG--GGGPfeelDLEDLRRVFEVNVFGPVRLT 121

protochlorophyllide reductase

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148670696  42 IVTGANTGIGKETAKDLAQRGA-RVYLACRDVDKGELAAREIQAVTGNSQVFvrKLDLADTKSIRAFAKDFLAEEKHLHL 120
Cdd:PLN00015   1 IITGASSGLGLATAKALAETGKwHVVMACRDFLKAERAAKSAGMPKDSYTVM--HLDLASLDSVRQFVDNFRRSGRPLDV 78

                         90       100       110
                 ....*....|....*....|....*....|..
gi 148670696 121 LINNAGVMMcPYSK----TADGFEMHIGVNHL 148
Cdd:PLN00015  79 LVCNAAVYL-PTAKeptfTADGFELSVGTNHL 109

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 148670696  41 AIVTGANTGIGKETAKDLAQRGARVYLACRDVDKGELAAreiQAVTGNSQVFVRKLDLADTKSIRAFAKDFLAEEKHLHL 120
Cdd:cd05233    1 ALVTGASSGIGRAIARRLAREGAKVVLADRNEEALAELA---AIEALGGNAVAVQADVSDEEDVEALVEEALEEFGRLDI 77

                         90       100       110
                 ....*....|....*....|....*....|.
gi 148670696 121 LINNAGVM-MCPYSK-TADGFEMHIGVNHLA 149
Cdd:cd05233   78 LVNNAGIArPGPLEElTDEDWDRVLDVNLTG 108

clavulanic acid dehydrogenase (CAD), classical (c) SDR; CAD catalyzes the NADP-dependent reduction of clavulanate-9-aldehyde to clavulanic acid, a beta-lactamase inhibitor. 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 148670696  36 LPGKVAIVTGANTGIGKETAKDLAQRGARVYLACRDVDKGELAAREIQAVTGnsQVFVRKLDLADTKSIRAFAKDFLAEE 115
Cdd:cd08934    1 LQGKVALVTGASSGIGEATARALAAEGAAVAIAARRVDRLEALADELEAEGG--KALVLELDVTDEQQVDAAVERTVEAL 78

                         90
                 ....*....|....
gi 148670696 116 KHLHLLINNAGVMM 129
Cdd:cd08934   79 GRLDILVNNAGIML 92

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148670696  39 KVAIVTGANTGIGKETAKDLAQRGARVYLACRDVDKGELAAREiqavtGNSQVFVRKLDLADTKSIRAFAKDFLAEEKHL 118
Cdd:cd05374    1 KVVLITGCSSGIGLALALALAAQGYRVIATARNPDKLESLGEL-----LNDNLEVLELDVTDEESIKAAVKEVIERFGRI 75

                         90
                 ....*....|
gi 148670696 119 HLLINNAGVM 128
Cdd:cd05374   76 DVLVNNAGYG 85

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 148670696  36 LPGKVAIVTGANTGIGKETAKDLAQRGARVYLACRDVDKGELAAREIQAVTGNS----QVFVRKLDladtkSIRAFAKDF 111
Cdd:cd05369    1 LKGKVAFITGGGTGIGKAIAKAFAELGASVAIAGRKPEVLEAAAEEISSATGGRahpiQCDVRDPE-----AVEAAVDET 75

                         90       100       110
                 ....*....|....*....|....*....|....*..
gi 148670696 112 LAEEKHLHLLINNA-GVMMCPYSK-TADGFEMHIGVN 146
Cdd:cd05369   76 LKEFGKIDILINNAaGNFLAPAESlSPNGFKTVIDID 112

beta-Keto acyl carrier protein reductase (BKR), involved in Type II FAS, classical (c) SDRs; This subgroup includes the Escherichai coli K12 BKR, FabG. BKR catalyzes the NADPH-dependent reduction of ACP in the first reductive step of de novo fatty acid synthesis (FAS). FAS consists of four elongation steps, which are repeated to extend the fatty acid chain through the addition of two-carbo units from malonyl acyl-carrier protein (ACP): condensation, reduction, dehydration, and a final reduction. Type II FAS, typical of plants and many bacteria, maintains these activities on discrete polypeptides, while type I FAS utilizes one or two multifunctional polypeptides. BKR resembles enoyl reductase, which catalyzes the second reduction step in FAS. SDRs are a functionally diverse family of oxidoreductases that have a single domain with structurally conserved Rossmann fold (alpha/beta folding pattern with a central beta-sheet) NAD(P)(H) binding region and a structurally diverse C-terminal region. Classical SDRs are typically about 250 residues long, while extended SDRS are approximately 350 residues. Sequence identity between different SDR enzymes are typically in the 15-30% range, but the enzymes share the Rossmann fold NAD binding motif and characteristic NAD-binding and catalytic sequence patterns. These enzymes have a 3-glycine N-terminal NAD(P)(H) binding pattern: TGxxxGxG in classical SDRs. Extended SDRs have additional elements in the C-terminal region, and typically have a TGXXGXXG cofactor binding motif. Complex (multidomain) SDRs such as ketoreductase domains of fatty acid synthase have a GGXGXXG NAD(P) binding motif and an altered active site motif (YXXXN). Fungal type type ketoacyl reductases have a TGXXXGX(1-2)G NAD(P)-binding motif. Some atypical SDRs have lost catalytic activity and/or have an unusual NAD(P) binding motif and missing or unusual active site residues. Reactions catalyzed within the SDR family include isomerization, decarboxylation, epimerization, C=N bond reduction, dehydratase activity, dehalogenation, Enoyl-CoA reduction, and carbonyl-alcohol oxidoreduction. A critical catalytic Tyr residue (Tyr-151, human 15-hydroxyprostaglandin dehydrogenase (15-PGDH) numbering), is often found in a conserved YXXXK pattern. In addition to the Tyr and Lys, there is often an upstream Ser (Ser-138, 15-PGDH numbering) and/or an Asn (Asn-107, 15-PGDH numbering) or additional Ser, contributing to the active site. Substrates for these enzymes include sugars, steroids, alcohols, and aromatic compounds. The standard reaction mechanism is a proton relay involving the conserved Tyr-151 and Lys-155, and well as Asn-111 (or Ser). Some SDR family members, including 17 beta-hydroxysteroid dehydrogenase contain an additional helix-turn-helix motif that is not generally found among SDRs.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148670696  39 KVAIVTGANTGIGKETAKDLAQRGARVYLACRDVDKGELAAREIQAvtGNSQVFVRKLDLADTKSIRAFAKDFLAEEKHL 118
Cdd:cd05333    1 KVALVTGASRGIGRAIALRLAAEGAKVAVTDRSEEAAAETVEEIKA--LGGNAAALEADVSDREAVEALVEKVEAEFGPV 78

                         90       100
                 ....*....|....*....|....
gi 148670696 119 HLLINNAGVmmcpyskTADGFEMH 142
Cdd:cd05333   79 DILVNNAGI-------TRDNLLMR 95

short chain dehydrogenase; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148670696  35 QLPGKVAIVTGANTGIGKETAKDLAQRGARVYLACRDVDKGELAAREIQAVTGnsqvfvRKLDLADTKSIRAFAKDFLAE 114
Cdd:PRK07825   2 DLRGKVVAITGGARGIGLATARALAALGARVAIGDLDEALAKETAAELGLVVG------GPLDVTDPASFAAFLDAVEAD 75

                         90
                 ....*....|....
gi 148670696 115 EKHLHLLINNAGVM 128
Cdd:PRK07825  76 LGPIDVLVNNAGVM 89

SDR family oxidoreductase;

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148670696  35 QLPGKVAIVTGANTGIGKETAKDLAQRGARVYLACRDVDKGELAAREIQAvTGNSQVFVRkLDLADTKSIRAFAKDFLAE 114
Cdd:PRK07774   3 RFDDKVAIVTGAAGGIGQAYAEALAREGASVVVADINAEGAERVAKQIVA-DGGTAIAVQ-VDVSDPDSAKAMADATVSA 80

                         90
                 ....*....|....
gi 148670696 115 EKHLHLLINNAGVM 128
Cdd:PRK07774  81 FGGIDYLVNNAAIY 94

hypothetical protein; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148670696  35 QLPGKVAIVTGANTGIGKETAKDLAQRGARVYLAcrDVDKGEL--AAREIQAvtGNSQVFVRKLDLADTKSIRAFAKDFL 112
Cdd:PRK06194   3 DFAGKVAVITGAASGFGLAFARIGAALGMKLVLA--DVQQDALdrAVAELRA--QGAEVLGVRTDVSDAAQVEALADAAL 78

                         90
                 ....*....|....*
gi 148670696 113 AEEKHLHLLINNAGV 127
Cdd:PRK06194  79 ERFGAVHLLFNNAGV 93

short chain dehydrogenase; Validated

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148670696  39 KVAIVTGANTGIGKETAKDLAQRGARVYLACRDVDKGE-LAAREIQAVtgnsqvfvrKLDLADTKSIRAFAKDFLAEEKH 117
Cdd:PRK06182   4 KVALVTGASSGIGKATARRLAAQGYTVYGAARRVDKMEdLASLGVHPL---------SLDVTDEASIKAAVDTIIAEEGR 74

                 ....*....
gi 148670696 118 LHLLINNAG 126
Cdd:PRK06182  75 IDVLVNNAG 83

SDR family oxidoreductase;

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148670696  38 GKVAIVTGANTGIGKETAKDLAQRGARVYLACRDVDKGELAAREIQAVTGnsQVFVRKLDLADTKSIRAFAKDFLAEEKH 117
Cdd:PRK05855 315 GKLVVVTGAGSGIGRETALAFAREGAEVVASDIDEAAAERTAELIRAAGA--VAHAYRVDVSDADAMEAFAEWVRAEHGV 392

                         90       100       110
                 ....*....|....*....|....*....|.
gi 148670696 118 LHLLINNAGVMMC-PYSKT-ADGFEMHIGVN 146
Cdd:PRK05855 393 PDIVVNNAGIGMAgGFLDTsAEDWDRVLDVN 423

putative beta-ketoacyl acyl carrier protein [ACP] reductase (BKR)-like, SDR; This subgroup resembles the SDR family, but does not have a perfect match to the NAD-binding motif or the catalytic tetrad characteristic of the SDRs. It includes the SDRs, Q9HYA2 from Pseudomonas aeruginosa PAO1 and APE0912 from Aeropyrum pernix K1. 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 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 148670696  38 GKVAIVTGANTGIGKETAKDLAQRGARVYLACRDVDKGELAAREIQAvtGNSQVFVRKLDLADTKSIRAFAKDFLAEEKH 117
Cdd:cd05344    1 GKVALVTAASSGIGLAIARALAREGARVAICARNRENLERAASELRA--GGAGVLAVVADLTDPEDIDRLVEKAGDAFGR 78

                 ....*....
gi 148670696 118 LHLLINNAG 126
Cdd:cd05344   79 VDILVNNAG 87

SDR family oxidoreductase;

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148670696  39 KVAIVTGANTGIGKETAKDLAQRGARVYLACRDVDKGELAAREIQAVtGNSQVFVRKLDLADTKSIRAFAKDFLAEEKHL 118
Cdd:PRK07832   1 KRCFVTGAASGIGRATALRLAAQGAELFLTDRDADGLAQTVADARAL-GGTVPEHRALDISDYDAVAAFAADIHAAHGSM 79

                 ....*....
gi 148670696 119 HLLINNAGV 127
Cdd:PRK07832  80 DVVMNIAGI 88

SDR family oxidoreductase;

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148670696  36 LPGKVAIVTGANTGIGKETAKDLAQRGARVYLACRDvdkGELAAREIQAVTGNSQVFVRKLDLADTKSIRAFAKDFLAEE 115
Cdd:PRK06138   3 LAGRVAIVTGAGSGIGRATAKLFAREGARVVVADRD---AEAAERVAAAIAAGGRAFARQGDVGSAEAVEALVDFVAARW 79

                         90
                 ....*....|..
gi 148670696 116 KHLHLLINNAGV 127
Cdd:PRK06138  80 GRLDVLVNNAGF 91

SDR family oxidoreductase;

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148670696  36 LPGKVAIVTGANTGIGKETAKDLAQRGARVYLACRDVDKGELAAREIQAvtGNSQVFVRkLDLADTKSIRAFAKDFLAEE 115
Cdd:PRK07231   3 LEGKVAIVTGASSGIGEGIARRFAAEGARVVVTDRNEEAAERVAAEILA--GGRAIAVA-ADVSDEADVEAAVAAALERF 79

                         90
                 ....*....|.
gi 148670696 116 KHLHLLINNAG 126
Cdd:PRK07231  80 GSVDILVNNAG 90

short chain dehydrogenase; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148670696  36 LPGKVAIVTGANTGIGKETAKDLAQRGARVYLACRDVDKGELAAREIqavtGNSQVFVRkLDLADTKSIRAFAKDFLAEE 115
Cdd:PRK08265   4 LAGKVAIVTGGATLIGAAVARALVAAGARVAIVDIDADNGAAVAASL----GERARFIA-TDITDDAAIERAVATVVARF 78

                         90
                 ....*....|....*..
gi 148670696 116 KHLHLLINNAgvmmCPY 132
Cdd:PRK08265  79 GRVDILVNLA----CTY 91

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 148670696  39 KVAIVTGANTGIGKETAKDLAQRGARVYLACRDVDKGelAAREIQAVTGNSQVFVRKLDLADTKSIRAFAKDFLAEEKHL 118
Cdd:cd05323    1 KVAIITGGASGIGLATAKLLLKKGAKVAILDRNENPG--AAAELQAINPKVKATFVQCDVTSWEQLAAAFKKAIEKFGRV 78

                 ....*....
gi 148670696 119 HLLINNAGV 127
Cdd:cd05323   79 DILINNAGI 87

human dehydrogenase/reductase (SDR family) member 1 (DHRS1) and human hydroxysteroid dehydrogenase-like protein 2 (HSDL2), classical (c) SDRs; This subgroup includes human DHRS1 and human HSDL2 and related proteins. These are members of the classical SDR family, with a canonical Gly-rich NAD-binding motif and the typical YXXXK active site motif. However, the rest of the catalytic tetrad is not strongly conserved. DHRS1 mRNA has been detected in many tissues, liver, heart, skeletal muscle, kidney and pancreas; a longer transcript is predominantly expressed in the liver , a shorter one in the heart. HSDL2 may play a part in fatty acid metabolism, as it is found in peroxisomes. SDRs are a functionally diverse family of oxidoreductases that have a single domain with a structurally conserved Rossmann fold (alpha/beta folding pattern with a central beta-sheet), an NAD(P)(H)-binding region, and a structurally diverse C-terminal region. Classical SDRs are typically about 250 residues long, while extended SDRS are approximately 350 residues. Sequence identity between different SDR enzymes are typically in the 15-30% range, but the enzymes share the Rossmann fold NAD-binding motif and characteristic NAD-binding and catalytic sequence patterns. These enzymes have a 3-glycine N-terminal NAD(P)(H)-binding pattern (typically, TGxxxGxG in classical SDRs and TGxxGxxG in extended SDRs), while substrate binding is in the C-terminal region. A critical catalytic Tyr residue (Tyr-151, human 15-hydroxyprostaglandin dehydrogenase (15-PGDH) numbering), is often found in a conserved YXXXK pattern. In addition to the Tyr and Lys, there is often an upstream Ser (Ser-138, 15-PGDH numbering) and/or an Asn (Asn-107, 15-PGDH numbering) or additional Ser, contributing to the active site. Substrates for these enzymes include sugars, steroids, alcohols, and aromatic compounds. The standard reaction mechanism is a proton relay involving the conserved Tyr and Lys, as well as Asn (or Ser). Some SDR family members, including 17 beta-hydroxysteroid dehydrogenase contain an additional helix-turn-helix motif that is not generally found among SDRs.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148670696  36 LPGKVAIVTGANTGIGKETAKDLAQRGARVYLACRDVDKG------------ELAAREIQAVTGnsQVFVRKLDLADTKS 103
Cdd:cd05338    1 LSGKVAFVTGASRGIGRAIALRLAKAGATVVVAAKTASEGdngsakslpgtiEETAEEIEAAGG--QALPIVVDVRDEDQ 78

                         90       100
                 ....*....|....*....|....
gi 148670696 104 IRAFAKDFLAEEKHLHLLINNAGV 127
Cdd:cd05338   79 VRALVEATVDQFGRLDILVNNAGA 102

L-iditol 2-dehydrogenase;

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148670696  36 LPGKVAIVTGANTGIGKETAKDLAQRGARVYLACRDVDKGELAAREIQAvtgnsQVFVRKLDLADTKSIRAFAKDFLAEE 115
Cdd:PRK07067   4 LQGKVALLTGAASGIGEAVAERYLAEGARVVIADIKPARARLAALEIGP-----AAIAVSLDVTRQDSIDRIVAAAVERF 78

                         90
                 ....*....|..
gi 148670696 116 KHLHLLINNAGV 127
Cdd:PRK07067  79 GGIDILFNNAAL 90

SDR family oxidoreductase;

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148670696  38 GKVAIVTGANTGIGKETAKDLAQRGAR-VYLACRDVDKGELAAREIQAVtgnsqvfvrKLDLADTKSIRAFAkdflAEEK 116
Cdd:PRK08264   6 GKVVLVTGANRGIGRAFVEQLLARGAAkVYAAARDPESVTDLGPRVVPL---------QLDVTDPASVAAAA----EAAS 72