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
                  ....*....|....*....|....*....|....*....|....*....
gi 1958746322 124 GKVVLVTGANSGIGFETAKSFALHGAHVILACRNMSRASEAVSRILEEW 172
Cdd:cd09809     1 GKVIIITGANSGIGFETARSFALHGAHVILACRNMSRASAAVSRILEEW 49

Two conserved tryptophans domain; also known as the WWP or rsp5 domain; around 40 amino acids; functions as an interaction module in a diverse set of signalling proteins; binds specific proline-rich sequences but at low affinities compared to other peptide recognition proteins such as antibodies and receptors; WW domains have a single groove formed by a conserved Trp and Tyr which recognizes a pair of residues of the sequence X-Pro; variable loops and neighboring domains confer specificity in this domain; there are five distinct groups based on binding: 1) PPXY motifs 2) the PPLP motif; 3) PGM motifs; 4) PSP or PTP motifs; 5) PR motifs.

                          10        20        30
                  ....*....|....*....|....*....|.
gi 1958746322  60 PYGWEQETDENGQVFFVDHINKRTTYLDPRL 90
Cdd:cd00201     1 PPGWEERWDPDGRVYYYNHNTKETQWEDPRE 31

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
                  ....*....|....*....|....*....|....*....|....*....
gi 1958746322 124 GKVVLVTGANSGIGFETAKSFALHGAHVILACRNMSRASEAVSRILEEW 172
Cdd:cd09809     1 GKVIIITGANSGIGFETARSFALHGAHVILACRNMSRASAAVSRILEEW 49

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
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1958746322 121 DFTGKVVLVTGANSGIGFETAKSFALHGAHVILACRNMSRASEAVSRILEE 171
Cdd:COG1028     3 RLKGKVALVTGGSSGIGRAIARALAAEGARVVITDRDAEALEAAAAELRAA 53

Two conserved tryptophans domain; also known as the WWP or rsp5 domain; around 40 amino acids; functions as an interaction module in a diverse set of signalling proteins; binds specific proline-rich sequences but at low affinities compared to other peptide recognition proteins such as antibodies and receptors; WW domains have a single groove formed by a conserved Trp and Tyr which recognizes a pair of residues of the sequence X-Pro; variable loops and neighboring domains confer specificity in this domain; there are five distinct groups based on binding: 1) PPXY motifs 2) the PPLP motif; 3) PGM motifs; 4) PSP or PTP motifs; 5) PR motifs.

                          10        20
                  ....*....|....*....|....*....
gi 1958746322  19 PPGWEERTTKDGWVYYANHTEEKTQWEHP 47
Cdd:cd00201     1 PPGWEERWDPDGRVYYYNHNTKETQWEDP 29

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

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*..
gi 1958746322 125 KVVLVTGANSGIGFETAKSFALHGAHVILACRNMSRASEAVSRILEE 171
Cdd:pfam00106   1 KVALVTGASSGIGRAIAKRLAKEGAKVVLVDRSEEKLEAVAKELGAL 47

Domain with 2 conserved Trp (W) residues; Also known as the WWP or rsp5 domain. Binds proline-rich polypeptides.

                           10        20        30
                   ....*....|....*....|....*....|...
gi 1958746322   58 DLPYGWEQETDENGQVFFVDHINKRTTYLDPRL 90
Cdd:smart00456   1 PLPPGWEERKDPDGRPYYYNHETKETQWEKPRE 33

This enzymatic domain is part of bacterial polyketide synthases; It catalyses the first step in the reductive modification of the beta-carbonyl centres in the growing polyketide chain. It uses NADPH to reduce the keto group to a hydroxy group.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*..
gi 1958746322  125 KVVLVTGANSGIGFETAKSFALHGA-HVILACRNMSRASEAVSRILE 170
Cdd:smart00822   1 GTYLITGGLGGLGRALARWLAERGArRLVLLSRSGPDAPGAAALLAE 47

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
                  ....*....|....*....|....*....|....*....|....*....
gi 1958746322 124 GKVVLVTGANSGIGFETAKSFALHGAHVILACRNMSRASEAVSRILEEW 172
Cdd:cd09809     1 GKVIIITGANSGIGFETARSFALHGAHVILACRNMSRASAAVSRILEEW 49

short chain dehydrogenase; Provisional

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 1958746322 121 DFTGKVVLVTGANSGIGFETAKSFALHGAHVILACRNMSRASEAVSRILEEWP 173
Cdd:PRK06197   13 DQSGRVAVVTGANTGLGYETAAALAAKGAHVVLAVRNLDKGKAAAARITAATP 65

oxidoreductase; Provisional

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1958746322 107 YDGSTTAMEILQGRDFTGKVVLVTGANSGIGFETAKSFALHGAHVILACRNMSRASEAVSRI 168
Cdd:PRK06196    9 FGAASTAEEVLAGHDLSGKTAIVTGGYSGLGLETTRALAQAGAHVIVPARRPDVAREALAGI 70

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
                  ....*....|....*....|....*....|....*....|....*
gi 1958746322 124 GKVVLVTGANSGIGFETAKSFALHGAHVILACRNMSRASEAVSRI 168
Cdd:cd09807     1 GKTVIITGANTGIGKETARELARRGARVIMACRDMAKCEEAAAEI 45

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
                  ....*....|....*....|....*....|....*....|....*.
gi 1958746322 123 TGKVVLVTGANSGIGFETAKSFALHGAHVILACRNMSRASEAVSRI 168
Cdd:COG4221     4 KGKVALITGASSGIGAATARALAAAGARVVLAARRAERLEALAAEL 49

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
                  ....*....|....*....|....*....|....*....|....*..
gi 1958746322 122 FTGKVVLVTGANSGIGFETAKSFALHGAHVILACRNMSRASEAVSRI 168
Cdd:cd05369     1 LKGKVAFITGGGTGIGKAIAKAFAELGASVAIAGRKPEVLEAAAEEI 47

11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1)-like, classical (c) SDRs; Human 11beta_HSD1 catalyzes the NADP(H)-dependent interconversion of cortisone and cortisol. This subgroup also includes human dehydrogenase/reductase SDR family member 7C (DHRS7C) and DHRS7B. These proteins have the GxxxGxG nucleotide binding motif and S-Y-K catalytic triad characteristic of the SDRs, but have an atypical C-terminal domain that contributes to homodimerization contacts. SDRs are a functionally diverse family of oxidoreductases that have a single domain with a structurally conserved Rossmann fold (alpha/beta folding pattern with a central beta-sheet), an NAD(P)(H)-binding region, and a structurally diverse C-terminal region. Classical SDRs are typically about 250 residues long, while extended SDRs are approximately 350 residues. Sequence identity between different SDR enzymes are typically in the 15-30% range, but the enzymes share the Rossmann fold NAD-binding motif and characteristic NAD-binding and catalytic sequence patterns. These enzymes catalyze a wide range of activities including the metabolism of steroids, cofactors, carbohydrates, lipids, aromatic compounds, and amino acids, and act in redox sensing. Classical SDRs have an TGXXX[AG]XG cofactor binding motif and a YXXXK active site motif, with the Tyr residue of the active site motif serving as a critical catalytic residue (Tyr-151, human 15-hydroxyprostaglandin dehydrogenase (15-PGDH) numbering). In addition to the Tyr and Lys, there is often an upstream Ser (Ser-138, 15-PGDH numbering) and/or an Asn (Asn-107, 15-PGDH numbering) contributing to the active site; while substrate binding is in the C-terminal region, which determines specificity. The standard reaction mechanism is a 4-pro-S hydride transfer and proton relay involving the conserved Tyr and Lys, a water molecule stabilized by Asn, and nicotinamide. Extended SDRs have additional elements in the C-terminal region, and typically have a TGXXGXXG cofactor binding motif. Complex (multidomain) SDRs such as ketoreductase domains of fatty acid synthase have a GGXGXXG NAD(P)-binding motif and an altered active site motif (YXXXN). Fungal type ketoacyl reductases have a TGXXXGX(1-2)G NAD(P)-binding motif. Some atypical SDRs have lost catalytic activity and/or have an unusual NAD(P)-binding motif and missing or unusual active site residues. Reactions catalyzed within the SDR family include isomerization, decarboxylation, epimerization, C=N bond reduction, dehydratase activity, dehalogenation, Enoyl-CoA reduction, and carbonyl-alcohol oxidoreduction.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1958746322 122 FTGKVVLVTGANSGIGFETAKSFALHGAHVILACRNMSRASEAVSRILEEWPLLP 176
Cdd:cd05332     1 LQGKVVIITGASSGIGEELAYHLARLGARLVLSARREERLEEVKSECLELGAPSP 55

SDR family oxidoreductase;

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1958746322 114 MEILQGRDFTGKVVLVTGANSGIGFETAKSFALHGAHVILACRNMSRASEAVSRI 168
Cdd:PRK06124    1 MSILQRFSLAGQVALVTGSARGLGFEIARALAGAGAHVLVNGRNAATLEAAVAAL 55

Two conserved tryptophans domain; also known as the WWP or rsp5 domain; around 40 amino acids; functions as an interaction module in a diverse set of signalling proteins; binds specific proline-rich sequences but at low affinities compared to other peptide recognition proteins such as antibodies and receptors; WW domains have a single groove formed by a conserved Trp and Tyr which recognizes a pair of residues of the sequence X-Pro; variable loops and neighboring domains confer specificity in this domain; there are five distinct groups based on binding: 1) PPXY motifs 2) the PPLP motif; 3) PGM motifs; 4) PSP or PTP motifs; 5) PR motifs.

                          10        20
                  ....*....|....*....|....*....
gi 1958746322  19 PPGWEERTTKDGWVYYANHTEEKTQWEHP 47
Cdd:cd00201     1 PPGWEERWDPDGRVYYYNHNTKETQWEDP 29

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

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*
gi 1958746322 127 VLVTGANSGIGFETAKSFALHGAHVILACRNMSRASEAVSRILEE 171
Cdd:COG5748     9 VIITGASSGVGLYAAKALADRGWHVIMACRDLEKAEAAAQELGIP 53

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

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1958746322 124 GKVVLVTGANSGIGFETAKSFALHGAHVILACRNMSRASEAVSRILEEWPLLPQQ 178
Cdd:cd08939     1 GKHVLITGGSSGIGKALAKELVKEGANVIIVARSESKLEEAVEEIEAEANASGQK 55

SDR family oxidoreductase;

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 1958746322 120 RDFTGKVVLVTGANSGIGFETAKSFALHGAHVILACRNMSRASEAVSRILEEWP 173
Cdd:PRK05854   10 PDLSGKRAVVTGASDGLGLGLARRLAAAGAEVILPVRNRAKGEAAVAAIRTAVP 63

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

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*..
gi 1958746322 125 KVVLVTGANSGIGFETAKSFALHGAHVILACRNMSRASEAVSRILEE 171
Cdd:pfam00106   1 KVALVTGASSGIGRAIAKRLAKEGAKVVLVDRSEEKLEAVAKELGAL 47

SDR family oxidoreductase;

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|...
gi 1958746322 122 FTGKVVLVTGANSGIGFETAKSFALHGAHVILACRNMSRASEA 164
Cdd:PRK06500    4 LQGKTALITGGTSGIGLETARQFLAEGARVAITGRDPASLEAA 46

3-keto steroid reductase, classical (c) SDRs; 3-keto steroid reductase (in concert with other enzymes) catalyzes NADP-dependent sterol C-4 demethylation, as part of steroid biosynthesis. 3-keto reductase is a classical SDR, with a well conserved canonical active site tetrad and fairly well conserved characteristic NAD-binding motif. SDRs are a functionally diverse family of oxidoreductases that have a single domain with a structurally conserved Rossmann fold (alpha/beta folding pattern with a central beta-sheet), an NAD(P)(H)-binding region, and a structurally diverse C-terminal region. Classical SDRs are typically about 250 residues long, while extended SDRs are approximately 350 residues. Sequence identity between different SDR enzymes are typically in the 15-30% range, but the enzymes share the Rossmann fold NAD-binding motif and characteristic NAD-binding and catalytic sequence patterns. These enzymes catalyze a wide range of activities including the metabolism of steroids, cofactors, carbohydrates, lipids, aromatic compounds, and amino acids, and act in redox sensing. Classical SDRs have an TGXXX[AG]XG cofactor binding motif and a YXXXK active site motif, with the Tyr residue of the active site motif serving as a critical catalytic residue (Tyr-151, human 15-hydroxyprostaglandin dehydrogenase (15-PGDH) numbering). In addition to the Tyr and Lys, there is often an upstream Ser (Ser-138, 15-PGDH numbering) and/or an Asn (Asn-107, 15-PGDH numbering) contributing to the active site; while substrate binding is in the C-terminal region, which determines specificity. The standard reaction mechanism is a 4-pro-S hydride transfer and proton relay involving the conserved Tyr and Lys, a water molecule stabilized by Asn, and nicotinamide. Extended SDRs have additional elements in the C-terminal region, and typically have a TGXXGXXG cofactor binding motif. Complex (multidomain) SDRs such as ketoreductase domains of fatty acid synthase have a GGXGXXG NAD(P)-binding motif and an altered active site motif (YXXXN). Fungal type ketoacyl reductases have a TGXXXGX(1-2)G NAD(P)-binding motif. Some atypical SDRs have lost catalytic activity and/or have an unusual NAD(P)-binding motif and missing or unusual active site residues. Reactions catalyzed within the SDR family include isomerization, decarboxylation, epimerization, C=N bond reduction, dehydratase activity, dehalogenation, Enoyl-CoA reduction, and carbonyl-alcohol oxidoreduction.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 1958746322 125 KVVLVTGANSGIGFETAKSF-----ALHGAHVILACRNMSRASEAVSRILEEWP 173
Cdd:cd08941     2 KVVLVTGANSGLGLAICERLlaeddENPELTLILACRNLQRAEAACRALLASHP 55

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
                  ....*....|....*....|....*....|....*....|....
gi 1958746322 125 KVVLVTGANSGIGFETAKSFALHGAHVILACRNMSRASEAVSRI 168
Cdd:cd05333     1 KVALVTGASRGIGRAIALRLAAEGAKVAVTDRSEEAAAETVEEI 44

short chain dehydrogenase; Provisional

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 1958746322 121 DFTGKVVLVTGANSGIGFETAKSFALHGAHVILACRNMSRASEAVSRILEEWP 173
Cdd:PRK07576    6 DFAGKNVVVVGGTSGINLGIAQAFARAGANVAVASRSQEKVDAAVAQLQQAGP 58

short chain dehydrogenase; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958746322 120 RDFTGKVVLVTGANSGIGFETAKSFALHGAHVILACRNMSRASEAVSRIleewpllpqqGRPqgqTGHPLGPSASSSKES 199
Cdd:PRK07825    1 DDLRGKVVAITGGARGIGLATARALAALGARVAIGDLDEALAKETAAEL----------GLV---VGGPLDVTDPASFAA 67

                  ....*..
gi 1958746322 200 FLTEVLD 206
Cdd:PRK07825   68 FLDAVEA 74

SDR family oxidoreductase;

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*..
gi 1958746322 124 GKVVLVTGANSGIGFETAKSFALHGAHVILACRNMSRASEAVSRILE 170
Cdd:PRK07201  371 GKVVLITGASSGIGRATAIKVAEAGATVFLVARNGEALDELVAEIRA 417

short chain dehydrogenase; Provisional

                          10        20        30
                  ....*....|....*....|....*....|....
gi 1958746322 124 GKVVLVTGANSGIGFETAKSFALHGAHVILACRN 157
Cdd:PRK07478    6 GKVAIITGASSGIGRAAAKLFAREGAKVVVGARR 39

SDR family oxidoreductase;

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 1958746322 121 DFTGKVVLVTGANSGIGFETAKSFALHGAHVILACRNMSRASEAVSRILEEWP 173
Cdd:PRK07062    5 QLEGRVAVVTGGSSGIGLATVELLLEAGASVAICGRDEERLASAEARLREKFP 57

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

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1958746322 121 DFTGKVVLVTGANSGIGFETAKSFALHGAHVILACRNMSRASEAVSRILEE 171
Cdd:PRK05557    2 SLEGKVALVTGASRGIGRAIAERLAAQGANVVINYASSEAGAEALVAEIGA 52

light-dependent protochlorophyllide reductase (LPOR)-like, classical (c)-like SDRs; Classical SDR-like subgroup containing LPOR and related proteins. Protochlorophyllide (Pchlide) reductases act in chlorophyll biosynthesis. There are distinct enzymes that catalyze Pchlide reduction in light or dark conditions. Light-dependent reduction is via an NADP-dependent SDR, LPOR. 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
                  ....*....|....*....|....*....|....*....|.
gi 1958746322 125 KVVLVTGANSGIGFETAKSFALHGA-HVILACRNMSRASEA 164
Cdd:cd09810     2 GTVVITGASSGLGLAAAKALARRGEwHVVMACRDFLKAEQA 42

SDR family oxidoreductase;

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 1958746322 120 RDFTGKVVLVTGANSGIGFETAKSFALHGAHVILACRNMSRASEAVSRI 168
Cdd:PRK05855  311 GPFSGKLVVVTGAGSGIGRETALAFAREGAEVVASDIDEAAAERTAELI 359

short chain dehydrogenase; Provisional

                          10        20        30
                  ....*....|....*....|....*....|....*....
gi 1958746322 121 DFTGKVVLVTGANSGIGFETAKSFALHGAHVILACRNMS 159
Cdd:PRK07060    6 DFSGKSVLVTGASSGIGRACAVALAQRGARVVAAARNAA 44

SDR family oxidoreductase;

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 1958746322 121 DFTGKVVLVTGANSGIGFETAKSFALHGAHVILACRNMSRASEAVSRILE 170
Cdd:PRK06172    4 TFSGKVALVTGGAAGIGRATALAFAREGAKVVVADRDAAGGEETVALIRE 53

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
                  ....*....|....*....|....*....|...
gi 1958746322 125 KVVLVTGANSGIGFETAKSFALHGAHVILACRN 157
Cdd:cd05374     1 KVVLITGCSSGIGLALALALAAQGYRVIATARN 33

SDR family oxidoreductase;

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*...
gi 1958746322 124 GKVVLVTGANSGIGFETAKSFALHGAHVILACRNmsraSEAVSRILEE 171
Cdd:PRK06139    7 GAVVVITGASSGIGQATAEAFARRGARLVLAARD----EEALQAVAEE 50

short chain dehydrogenase; Provisional

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*..
gi 1958746322 111 TTAMEILQGRDFTGKVVLVTGANSGIGFETAKSFALHGAHVILACRN 157
Cdd:PRK06841    2 TDTKQFDLAFDLSGKVAVVTGGASGIGHAIAELFAAKGARVALLDRS 48

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
                  ....*....|....*....|....*....|....*....|....*...
gi 1958746322 124 GKVVLVTGANSGIGFETAKSFALHGAHVILACRNMSRASEAVSRILEE 171
Cdd:cd09808     1 GRSFLITGANSGIGKAAALAIAKRGGTVHMVCRNQTRAEEARKEIETE 48

SDR family oxidoreductase;

                          10        20        30
                  ....*....|....*....|....*....|....*..
gi 1958746322 124 GKVVLVTGANSGIGFETAKSFALHGAHVILACRNMSR 160
Cdd:PRK06181    1 GKVVIITGASEGIGRALAVRLARAGAQLVLAARNETR 37

SDR family oxidoreductase;

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1958746322 121 DFTGKVVLVTGANSGIGFETAKSFALHGAHVILACRNMSRASEAVSRILEE 171
Cdd:PRK07806    3 DLPGKTALVTGSSRGIGADTAKILAGAGAHVVVNYRQKAPRANKVVAEIEA 53

L-iditol 2-dehydrogenase;

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*
gi 1958746322 124 GKVVLVTGANSGIGFETAKSFALHGAHVILACRNMSRASEAVSRI 168
Cdd:PRK07067    6 GKVALLTGAASGIGEAVAERYLAEGARVVIADIKPARARLAALEI 50

gluconate 5-dehydrogenase; Provisional

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*...
gi 1958746322 121 DFTGKVVLVTGANSGIGFETAKSFALHGAHVILACRNMSRASEAVSRI 168
Cdd:PRK07523    7 DLTGRRALVTGSSQGIGYALAEGLAQAGAEVILNGRDPAKLAAAAESL 54

classical (c) SDR, subgroup 5; These proteins are members of the classical SDR family, with a canonical active site tetrad and a typical Gly-rich NAD-binding motif. SDRs are a functionally diverse family of oxidoreductases that have a single domain with a structurally conserved Rossmann fold (alpha/beta folding pattern with a central beta-sheet), an NAD(P)(H)-binding region, and a structurally diverse C-terminal region. Classical SDRs are typically about 250 residues long, while extended SDRs are approximately 350 residues. Sequence identity between different SDR enzymes are typically in the 15-30% range, but the enzymes share the Rossmann fold NAD-binding motif and characteristic NAD-binding and catalytic sequence patterns. These enzymes catalyze a wide range of activities including the metabolism of steroids, cofactors, carbohydrates, lipids, aromatic compounds, and amino acids, and act in redox sensing. Classical SDRs have an TGXXX[AG]XG cofactor binding motif and a YXXXK active site motif, with the Tyr residue of the active site motif serving as a critical catalytic residue (Tyr-151, human 15-hydroxyprostaglandin dehydrogenase (15-PGDH) numbering). In addition to the Tyr and Lys, there is often an upstream Ser (Ser-138, 15-PGDH numbering) and/or an Asn (Asn-107, 15-PGDH numbering) contributing to the active site; while substrate binding is in the C-terminal region, which determines specificity. The standard reaction mechanism is a 4-pro-S hydride transfer and proton relay involving the conserved Tyr and Lys, a water molecule stabilized by Asn, and nicotinamide. Extended SDRs have additional elements in the C-terminal region, and typically have a TGXXGXXG cofactor binding motif. Complex (multidomain) SDRs such as ketoreductase domains of fatty acid synthase have a GGXGXXG NAD(P)-binding motif and an altered active site motif (YXXXN). Fungal type ketoacyl reductases have a TGXXXGX(1-2)G NAD(P)-binding motif. Some atypical SDRs have lost catalytic activity and/or have an unusual NAD(P)-binding motif and missing or unusual active site residues. Reactions catalyzed within the SDR family include isomerization, decarboxylation, epimerization, C=N bond reduction, dehydratase activity, dehalogenation, Enoyl-CoA reduction, and carbonyl-alcohol oxidoreduction.

                          10        20        30
                  ....*....|....*....|....*....|....*.
gi 1958746322 125 KVVLVTGANSGIGFETAKSFALHGAHVILACRNMSR 160
Cdd:cd05346     1 KTVLITGASSGIGEATARRFAKAGAKLILTGRRAER 36

carbonyl reductase sniffer-like, classical (c) SDRs; Sniffer is an NADPH-dependent carbonyl reductase of the classical SDR family. Studies in Drosophila melanogaster implicate Sniffer in the prevention of neurodegeneration due to aging and oxidative-stress. This subgroup also includes Rhodococcus sp. AD45 IsoH, which is an NAD-dependent 1-hydroxy-2-glutathionyl-2-methyl-3-butene dehydrogenase involved in isoprene metabolism, Aspergillus nidulans StcE encoded by a gene which is part of a proposed sterigmatocystin biosynthesis gene cluster, Bacillus circulans SANK 72073 BtrF encoded by a gene found in the butirosin biosynthesis gene cluster, and Aspergillus parasiticus nor-1 involved in the biosynthesis of aflatoxins. 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
                  ....*....|....*....|....*....|....*...
gi 1958746322 127 VLVTGANSGIGFETAKSFALHG-AHVILACRNMSRASE 163
Cdd:cd05325     1 VLITGASRGIGLELVRQLLARGnNTVIATCRDPSAATE 38

classical (c) SDR, subgroup 7; These proteins are members of the classical SDR family, with a canonical active site triad (and also an active site Asn) 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 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
                  ....*....|....*....|....*....|....*....|....*
gi 1958746322 122 FTGKVVLVTGANSGIGFETAKSFALHGA-HVILACRNMSRASEAV 165
Cdd:cd05354     1 IKDKTVLVTGANRGIGKAFVESLLAHGAkKVYAAVRDPGSAAHLV 45

xylulose reductase-like, classical (c) SDRs; Members of this subgroup include proteins identified as L-xylulose reductase (XR) and carbonyl reductase; they are members of the SDR family. XR, catalyzes the NADP-dependent reduction of L-xyulose and other sugars. Tetrameric mouse carbonyl reductase is involved in the metabolism of biogenic and xenobiotic carbonyl compounds. This subgroup also includes tetrameric chicken liver D-erythrulose reductase, which catalyzes the reduction of D-erythrulose to D-threitol. 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).

                          10        20        30
                  ....*....|....*....|....*....|....*..
gi 1958746322 121 DFTGKVVLVTGANSGIGFETAKSFALHGAHVILACRN 157
Cdd:cd05351     4 DFAGKRALVTGAGKGIGRATVKALAKAGARVVAVSRT 40

SDR family oxidoreductase;

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....
gi 1958746322 122 FTGKVVLVTGANSGIGFETAKSFALHGAHVILACRNMSRASEAV 165
Cdd:PRK07326    4 LKGKVALITGGSKGIGFAIAEALLAEGYKVAITARDQKELEEAA 47

SDR family oxidoreductase;

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 1958746322 121 DFTGKVVLVTGANSGIGFETAKSFALHGAHVILACRNMSRASEAVSRILE 170
Cdd:PRK06138    2 RLAGRVAIVTGAGSGIGRATAKLFAREGARVVVADRDAEAAERVAAAIAA 51

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
                  ....*....|....*....|....*....|....*....|....*.
gi 1958746322 123 TGKVVLVTGANSGIGFETAKSFALHGAHVILACRNMSRASEAVSRI 168
Cdd:cd08934     2 QGKVALVTGASSGIGEATARALAAEGAAVAIAARRVDRLEALADEL 47

short chain dehydrogenase; Provisional

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 1958746322 123 TGKVVLVTGANSGIGFETAKSFALHGAHVILACRNMSRASEAVSRILEE 171
Cdd:PRK12939    6 AGKRALVTGAARGLGAAFAEALAEAGATVAFNDGLAAEARELAAALEAA 54

1,6-dihydroxycyclohexa-2,4-diene-1-carboxylate dehydrogenase; Provisional

                          10        20        30        40        50
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gi 1958746322 122 FTGKVVLVTGANSGIGFETAKSFALHGAHVILACRnmsraSEAVSRILEE 171
Cdd:PRK12823    6 FAGKVVVVTGAAQGIGRGVALRAAAEGARVVLVDR-----SELVHEVAAE 50

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.

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gi 1958746322 124 GKVVLVTGANSGIGFETAKSFALHGAHVILA 154
Cdd:cd05326     4 GKVAIITGGASGIGEATARLFAKHGARVVIA 34

enoyl-[acyl-carrier-protein] reductase FabL;

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gi 1958746322 122 FTGKVVLVTGANSGIGFETAKSFALHGAHVILacrNMSRASEAVSRILEEwplLPQQGR 180
Cdd:PRK08063    2 FSGKVALVTGSSRGIGKAIALRLAEEGYDIAV---NYARSRKAAEETAEE---IEALGR 54