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        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1443057682  36 GRHVLITGGSSGIGLAMATAAAREGARVSILARNAARLEEARGAIRAATGRD---VGVHAADVRDADAVARALAEA---- 108
Cdd:cd08939     1 GKHVLITGGSSGIGKALAKELVKEGANVIIVARSESKLEEAVEEIEAEANASgqkVSYISADLSDYEEVEQAFAQAvekg 80

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1443057682 109 GPVDVLVCNHGVFVPQELEKQEMEEVKWMVDINLMGTFHLVKAALPAMKERTketrlPASIAIMSSQAGQ 178
Cdd:cd08939    81 GPPDLVVNCAGISIPGLFEDLTAEEFERGMDVNYFGSLNVAHAVLPLMKEQR-----PGHIVFVSSQAAL 145

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1443057682  37 RHVLITGGSSGIGLAMATAAAREGARVSILARNAARLEEARGAIRAATGRDVGVhAADVRDADAVARALAEA----GPVD 112
Cdd:pfam00106   1 KVALVTGASSGIGRAIAKRLAKEGAKVVLVDRSEEKLEAVAKELGALGGKALFI-QGDVTDRAQVKALVEQAverlGRLD 79

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1443057682 113 VLVCNHGVFVPQELEKQEMEEVKWMVDINLMGTFHLVKAALPAMKERTKetrlpASIAIMSSQAGQ 178
Cdd:pfam00106  80 ILVNNAGITGLGPFSELSDEDWERVIDVNLTGVFNLTRAVLPAMIKGSG-----GRIVNISSVAGL 140

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        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1443057682  36 GRHVLITGGSSGIGLAMATAAAREGARVSILARNAARLEEARGAIRAATGRD---VGVHAADVRDADAVARALAEA---- 108
Cdd:cd08939     1 GKHVLITGGSSGIGKALAKELVKEGANVIIVARSESKLEEAVEEIEAEANASgqkVSYISADLSDYEEVEQAFAQAvekg 80

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1443057682 109 GPVDVLVCNHGVFVPQELEKQEMEEVKWMVDINLMGTFHLVKAALPAMKERTketrlPASIAIMSSQAGQ 178
Cdd:cd08939    81 GPPDLVVNCAGISIPGLFEDLTAEEFERGMDVNYFGSLNVAHAVLPLMKEQR-----PGHIVFVSSQAAL 145

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 1443057682  39 VLITGGSSGIGLAMATAAAREGARVSILARNAARLEEArgAIRAATGRDVGVHAADVRDADAVARALAEA----GPVDVL 114
Cdd:cd05233     1 ALVTGASSGIGRAIARRLAREGAKVVLADRNEEALAEL--AAIEALGGNAVAVQADVSDEEDVEALVEEAleefGRLDIL 78

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1443057682 115 VCNHGVFVPQELEKQEMEEVKWMVDINLMGTFHLVKAALPAMKERTKetrlpASIAIMSSQAGQRAN 181
Cdd:cd05233    79 VNNAGIARPGPLEELTDEDWDRVLDVNLTGVFLLTRAALPHMKKQGG-----GRIVNISSVAGLRPL 140

3-oxoacyl-ACP reductase FabG;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1443057682  34 LKGRHVLITGGSSGIGLAMATAAAREGARVSILARNAARLEEARGAIRAATGRDVGVhAADVRDADAVARALAEA----G 109
Cdd:PRK05653    3 LQGKTALVTGASRGIGRAIALRLAADGAKVVIYDSNEEAAEALAAELRAAGGEARVL-VFDVSDEAAVRALIEAAveafG 81

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1443057682 110 PVDVLVCNHGVFVPQELEKQEMEEVKWMVDINLMGTFHLVKAALPAMKERTKetrlpASIAIMSSQAGQRAN 181
Cdd:PRK05653   82 ALDILVNNAGITRDALLPRMSEEDWDRVIDVNLTGTFNVVRAALPPMIKARY-----GRIVNISSVSGVTGN 148

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        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1443057682  34 LKGRHVLITGGSSGIGLAMATAAAREGARVSILARNAARLEEARGAIRAATGRDVGVHAADVRDADAVARALAEA----G 109
Cdd:cd05332     1 LQGKVVIITGASSGIGEELAYHLARLGARLVLSARREERLEEVKSECLELGAPSPHVVPLDMSDLEDAEQVVEEAlklfG 80

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1443057682 110 PVDVLVCNHGVFVPQELEKQEMEEVKWMVDINLMGTFHLVKAALPAMKERTKetrlpASIAIMSSQAG 177
Cdd:cd05332    81 GLDILINNAGISMRSLFHDTSIDVDRKIMEVNYFGPVALTKAALPHLIERSQ-----GSIVVVSSIAG 143

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1443057682  33 PLKGRHVLITGGSSGIGLAMATAAAREGARVSILAR-NAARLEEARGAIRAAtGRDVGVHAADVRDADAVARALAEA--- 108
Cdd:PRK12825    3 SLMGRVALVTGAARGLGRAIALRLARAGADVVVHYRsDEEAAEELVEAVEAL-GRRAQAVQADVTDKAALEAAVAAAver 81

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1443057682 109 -GPVDVLVCNHGVFVPQELEkqEMEEVKW--MVDINLMGTFHLVKAALPAMKERTKetrlpASIAIMSSQAGQRAN 181
Cdd:PRK12825   82 fGRIDILVNNAGIFEDKPLA--DMSDDEWdeVIDVNLSGVFHLLRAVVPPMRKQRG-----GRIVNISSVAGLPGW 150

SDR family oxidoreductase;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1443057682  34 LKGRHVLITGGSSGIGLAMATAAAREGARVSILARNAARLEEARGAIRAAtGRDVGVhAADVRDADAVARA----LAEAG 109
Cdd:PRK07326    4 LKGKVALITGGSKGIGFAIAEALLAEGYKVAITARDQKELEEAAAELNNK-GNVLGL-AADVRDEADVQRAvdaiVAAFG 81

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|
gi 1443057682 110 PVDVLVCNHGVFVPQELEKQEMEEVKWMVDINLMGTFHLVKAALPAMKER 159
Cdd:PRK07326   82 GLDVLIANAGVGHFAPVEELTPEEWRLVIDTNLTGAFYTIKAAVPALKRG 131

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1443057682  34 LKGRHVLITGGSSGIGLAMATAAAREGARVSILARNAARLEEARGAIrAATGRDVGVHAADVRDAD----AVARALAEAG 109
Cdd:PRK07666    5 LQGKNALITGAGRGIGRAVAIALAKEGVNVGLLARTEENLKAVAEEV-EAYGVKVVIATADVSDYEevtaAIEQLKNELG 83

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1443057682 110 PVDVLVCNHGVFVPQELEKQEMEEVKWMVDINLMGTFHLVKAALPAMKERTKetrlpASIAIMSSQAGQR 179
Cdd:PRK07666   84 SIDILINNAGISKFGKFLELDPAEWEKIIQVNLMGVYYATRAVLPSMIERQS-----GDIINISSTAGQK 148

mannitol dehydrogenase (MDH)-like, classical (c) SDRs; NADP-mannitol dehydrogenase catalyzes the conversion of fructose to mannitol, an acyclic 6-carbon sugar. MDH is a tetrameric member of the SDR family. This subgroup also includes various other tetrameric SDRs, including Pichia stipitis D-arabinitol dehydrogenase (aka polyol dehydrogenase), Candida albicans Sou1p, a sorbose reductase, and Candida parapsilosis (S)-specific carbonyl reductase (SCR, aka S-specific alcohol dehydrogenase) which catalyzes the enantioselective reduction of 2-hydroxyacetophenone into (S)-1-phenyl-1,2-ethanediol. 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        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1443057682  34 LKGRHVLITGGSSGIGLAMATAAAREGARVSILARNAARLEEARGAIRAATGRDVGVHAADVRDADAVARALAEA----G 109
Cdd:cd05352     6 LKGKVAIVTGGSRGIGLAIARALAEAGADVAIIYNSAPRAEEKAEELAKKYGVKTKAYKCDVSSQESVEKTFKQIqkdfG 85

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1443057682 110 PVDVLVCNHGVFVPQELEKQEMEEVKWMVDINLMGTFHLVKAALPAMKERTKetrlpASIAIMSSQAGQRAN 181
Cdd:cd05352    86 KIDILIANAGITVHKPALDYTYEQWNKVIDVNLNGVFNCAQAAAKIFKKQGK-----GSLIITASMSGTIVN 152

SDR family oxidoreductase;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1443057682  34 LKGRHVLITGGSSGIGLAMATAAAREGARVSILARNAARLEEARGAIRAAtGRDVGVhAADVRDADAVARALAEA----G 109
Cdd:PRK07231    3 LEGKVAIVTGASSGIGEGIARRFAAEGARVVVTDRNEEAAERVAAEILAG-GRAIAV-AADVSDEADVEAAVAAAlerfG 80

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1443057682 110 PVDVLVCNHGVF-VPQELEKQEMEEVKWMVDINLMGTFHLVKAALPAMKERTKetrlpASIAIMSSQAGQRAN 181
Cdd:PRK07231   81 SVDILVNNAGTThRNGPLLDVDEAEFDRIFAVNVKSPYLWTQAAVPAMRGEGG-----GAIVNVASTAGLRPR 148

3-hydroxybutyrate dehydrogenase; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1443057682  34 LKGRHVLITGGSSGIGLAMATAAAREGARVSILARNAARLEEARGAIRAAtGRDVGVHAADVRDADAVARALAEA----G 109
Cdd:PRK12429    2 LKGKVALVTGAASGIGLEIALALAKEGAKVVIADLNDEAAAAAAEALQKA-GGKAIGVAMDVTDEEAINAGIDYAvetfG 80

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|
gi 1443057682 110 PVDVLVCNHGVFVPQELEKQEMEEVKWMVDINLMGTFHLVKAALPAMKER 159
Cdd:PRK12429   81 GVDILVNNAGIQHVAPIEDFPTEKWKKMIAIMLDGAFLTTKAALPIMKAQ 130

short chain dehydrogenase; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1443057682  33 PLKGRHVLITGGSSGIGLAMATAAAREGARVSILARNAARLEEARGAIRAATGRDVGVhAADVRDADAVARALAEA---- 108
Cdd:PRK07109    5 PIGRQVVVITGASAGVGRATARAFARRGAKVVLLARGEEGLEALAAEIRAAGGEALAV-VADVADAEAVQAAADRAeeel 83

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1443057682 109 GPVDVLVCNHGVFVPQELEKQEMEEVKWMVDINLMGTFHLVKAALPAMKER 159
Cdd:PRK07109   84 GPIDTWVNNAMVTVFGPFEDVTPEEFRRVTEVTYLGVVHGTLAALRHMRPR 134

SDR family oxidoreductase;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1443057682  34 LKGRHVLITGGSSGIGLAMATAAAREGARVSILARNAARLEEArgaiRAATGRDVGV---HAADVRDADAVARALAEAGP 110
Cdd:PRK06500    4 LQGKTALITGGTSGIGLETARQFLAEGARVAITGRDPASLEAA----RAELGESALViraDAGDVAAQKALAQALAEAFG 79

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1443057682 111 -VDVLVCNHGVFVPQELEkqEMEEVKW--MVDINLMGTFHLVKAALPAMKErtketrlPASIAIMSS 174
Cdd:PRK06500   80 rLDAVFINAGVAKFAPLE--DWDEAMFdrSFNTNVKGPYFLIQALLPLLAN-------PASIVLNGS 137

retinol dehydrogenase (retinol-DH), Light dependent Protochlorophyllide (Pchlide) OxidoReductase (LPOR) and related proteins, classical (c) SDRs; Classical SDR subgroup containing retinol-DHs, LPORs, and related proteins. Retinol is processed by a medium chain alcohol dehydrogenase followed by retinol-DHs. 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. This subgroup includes the human proteins: retinol dehydrogenase -12, -13 ,and -14, dehydrogenase/reductase SDR family member (DHRS)-12 , -13 and -X (a DHRS on chromosome X), and WWOX (WW domain-containing oxidoreductase), as well as a Neurospora crassa SDR encoded by the blue light inducible bli-4 gene. 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 1443057682  36 GRHVLITGGSSGIGLAMATAAAREGARVSILARNAARLEEARGAIRAATGRD-VGVHAADVRDADAVARA----LAEAGP 110
Cdd:cd05327     1 GKVVVITGANSGIGKETARELAKRGAHVIIACRNEEKGEEAAAEIKKETGNAkVEVIQLDLSSLASVRQFaeefLARFPR 80

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1443057682 111 VDVLVCNHGVFVPQELEKQEMEEVKWMVdiNLMGTFHLVKAALPAMKeRTKETRlpasIAIMSSQAGQRANLRFVD 186
Cdd:cd05327    81 LDILINNAGIMAPPRRLTKDGFELQFAV--NYLGHFLLTNLLLPVLK-ASAPSR----IVNVSSIAHRAGPIDFND 149

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1443057682  34 LKGRHVLITGGSSGIGLAMATAAAREGARVSILARNAARLEEARGAIRAATGRDVGVHAADVRDADAVARALAEA----G 109
Cdd:PRK05557    3 LEGKVALVTGASRGIGRAIAERLAAQGANVVINYASSEAGAEALVAEIGALGGKALAVQGDVSDAESVERAVDEAkaefG 82

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|
gi 1443057682 110 PVDVLVCNHGVFVPQELEKQEMEEVKWMVDINLMGTFHLVKAALPAMKER 159
Cdd:PRK05557   83 GVDILVNNAGITRDNLLMRMKEEDWDRVIDTNLTGVFNLTKAVARPMMKQ 132

SDR family oxidoreductase;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1443057682  33 PLKGRHVLITGGSSGIGLAMATAAAREGARVSILARNA---ARLE----EARGAIRAATGRDVGVhAADVRDADAVARAL 105
Cdd:PRK08278    3 SLSGKTLFITGASRGIGLAIALRAARDGANIVIAAKTAephPKLPgtihTAAEEIEAAGGQALPL-VGDVRDEDQVAAAV 81

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 1443057682 106 AEA----GPVDVLVCNHGVFVPQELEKQEMEEVKWMVDINLMGTFHLVKAALPAMKER 159
Cdd:PRK08278   82 AKAverfGGIDICVNNASAINLTGTEDTPMKRFDLMQQINVRGTFLVSQACLPHLKKS 139

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1443057682  34 LKGRHVLITGGSSGIGLAMATAAAREGARVSI--LARNAARLEEARGAIRAAtGRDVGVHAADVRD----ADAVARALAE 107
Cdd:cd05355    24 LKGKKALITGGDSGIGRAVAIAFAREGADVAInyLPEEEDDAEETKKLIEEE-GRKCLLIPGDLGDesfcRDLVKEVVKE 102

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1443057682 108 AGPVDVLVCNHGVFVPQE-LEKQEMEEVKWMVDINLMGTFHLVKAALPAMKE 158
Cdd:cd05355   103 FGKLDILVNNAAYQHPQEsIEDITTEQLEKTFRTNIFSMFYLTKAALPHLKK 154

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 1443057682  34 LKGRHVLITGGSSGIGLAMATAAAREGARVSILARNAARLEEARGAIRAATGRdVGVHAADVRDA----DAVARALAEAG 109
Cdd:cd08934     1 LQGKVALVTGASSGIGEATARALAAEGAAVAIAARRVDRLEALADELEAEGGK-ALVLELDVTDEqqvdAAVERTVEALG 79

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1443057682 110 PVDVLVCNHGVFVPQELEKQEMEEVKWMVDINLMGTFHLVKAALPAMKERTKetrlpASIAIMSSQAGQRA 180
Cdd:cd08934    80 RLDILVNNAGIMLLGPVEDADTTDWTRMIDTNLLGLMYTTHAALPHHLLRNK-----GTIVNISSVAGRVA 145

3beta17beta hydroxysteroid dehydrogenase-like, classical (c) SDRs; This subgroup includes members identified as 3beta17beta hydroxysteroid dehydrogenase, 20beta hydroxysteroid dehydrogenase, and R-alcohol dehydrogenase. These proteins exhibit the canonical active site tetrad and glycine rich NAD(P)-binding motif of the classical SDRs. 17beta-dehydrogenases are a group of isozymes that catalyze activation and inactivation of estrogen and androgens, and include members of the SDR family. SDRs are a functionally diverse family of oxidoreductases that have a single domain with a structurally conserved Rossmann fold (alpha/beta folding pattern with a central beta-sheet), an NAD(P)(H)-binding region, and a structurally diverse C-terminal region. Classical SDRs are typically about 250 residues long, while extended SDRS are approximately 350 residues. Sequence identity between different SDR enzymes are typically in the 15-30% range, but the enzymes share the Rossmann fold NAD-binding motif and characteristic NAD-binding and catalytic sequence patterns. These enzymes have a 3-glycine N-terminal NAD(P)(H)-binding pattern (typically, TGxxxGxG in classical SDRs and TGxxGxxG in extended SDRs), while substrate binding is in the C-terminal region. A critical catalytic Tyr residue (Tyr-151, human 15-hydroxyprostaglandin dehydrogenase (15-PGDH) numbering), is often found in a conserved YXXXK pattern. In addition to the Tyr and Lys, there is often an upstream Ser (Ser-138, 15-PGDH numbering) and/or an Asn (Asn-107, 15-PGDH numbering) or additional Ser, contributing to the active site. Substrates for these enzymes include sugars, steroids, alcohols, and aromatic compounds. The standard reaction mechanism is a proton relay involving the conserved Tyr and Lys, as well as Asn (or Ser). Some SDR family members, including 17 beta-hydroxysteroid dehydrogenase contain an additional helix-turn-helix motif that is not generally found among SDRs.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1443057682  34 LKGRHVLITGGSSGIGLAMATAAAREGARVSIlarnAARLEEARGAIRAATGRDVGVHAADVRDAD----AVARALAEAG 109
Cdd:cd05341     3 LKGKVAIVTGGARGLGLAHARLLVAEGAKVVL----SDILDEEGQAAAAELGDAARFFHLDVTDEDgwtaVVDTAREAFG 78

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1443057682 110 PVDVLVCNHGVFVPQELEKQEMEEVKWMVDINLMGTFHLVKAALPAMKERTKetrlpASIAIMSSQAG 177
Cdd:cd05341    79 RLDVLVNNAGILTGGTVETTTLEEWRRLLDINLTGVFLGTRAVIPPMKEAGG-----GSIINMSSIEG 141