3-hydroxybutyrate dehydrogenase; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1895054273   1 AGGKAIGVAMDVTNEDAVNAGIDKVAAEFGSVDILVSNAGIQIVNPIENYSFSDWKKMQAIHVDGAFLTTKAALKHMYKD 80
Cdd:PRK13394   54 AGGKAIGVAMDVTNEDAVNAGIDKVAERFGSVDILVSNAGIQIVNPIENYSFADWKKMQAIHVDGAFLTTKAALKHMYKD 133

                          90       100       110
                  ....*....|....*....|....*....|...
gi 1895054273  81 DRGGVVIYMGSVHSHEASPLKSAYVTAKHGLLG 113
Cdd:PRK13394  134 DRGGVVIYMGSVHSHEASPLKSAYVTAKHGLLG 166

3-hydroxybutyrate dehydrogenase; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1895054273   1 AGGKAIGVAMDVTNEDAVNAGIDKVAAEFGSVDILVSNAGIQIVNPIENYSFSDWKKMQAIHVDGAFLTTKAALKHMYKD 80
Cdd:PRK13394   54 AGGKAIGVAMDVTNEDAVNAGIDKVAERFGSVDILVSNAGIQIVNPIENYSFADWKKMQAIHVDGAFLTTKAALKHMYKD 133

                          90       100       110
                  ....*....|....*....|....*....|...
gi 1895054273  81 DRGGVVIYMGSVHSHEASPLKSAYVTAKHGLLG 113
Cdd:PRK13394  134 DRGGVVIYMGSVHSHEASPLKSAYVTAKHGLLG 166

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 1895054273   1 AGGKAIGVAMDVTNEDAVNAGIDKVAAEFGSVDILVSNAGIQIVNPIENYSFSDWKKMQAIHVDGAFLTTKAALKHMyKD 80
Cdd:cd05233    44 LGGNAVAVQADVSDEEDVEALVEEALEEFGRLDILVNNAGIARPGPLEELTDEDWDRVLDVNLTGVFLLTRAALPHM-KK 122

                          90       100       110
                  ....*....|....*....|....*....|...
gi 1895054273  81 DRGGVVIYMGSVHSHEASPLKSAYVTAKHGLLG 113
Cdd:cd05233   123 QGGGRIVNISSVAGLRPLPGQAAYAASKAALEG 155

3-hydroxybutyrate dehydrogenase; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1895054273   1 AGGKAIGVAMDVTNEDAVNAGIDKVAAEFGSVDILVSNAGIQIVNPIENYSFSDWKKMQAIHVDGAFLTTKAALKHMYKD 80
Cdd:PRK13394   54 AGGKAIGVAMDVTNEDAVNAGIDKVAERFGSVDILVSNAGIQIVNPIENYSFADWKKMQAIHVDGAFLTTKAALKHMYKD 133

                          90       100       110
                  ....*....|....*....|....*....|...
gi 1895054273  81 DRGGVVIYMGSVHSHEASPLKSAYVTAKHGLLG 113
Cdd:PRK13394  134 DRGGVVIYMGSVHSHEASPLKSAYVTAKHGLLG 166

NAD(P)-dependent dehydrogenase, short-chain alcohol dehydrogenase family [Lipid transport and metabolism]; NAD(P)-dependent dehydrogenase, short-chain alcohol dehydrogenase family is part of the Pathway/BioSystem: Fatty acid biosynthesis

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1895054273   1 AGGKAIGVAMDVTNEDAVNAGIDKVAAEFGSVDILVSNAGIQIVNPIENYSFSDWKKMQAIHVDGAFLTTKAALKHMyKD 80
Cdd:COG1028    53 AGGRALAVAADVTDEAAVEALVAAAVAAFGRLDILVNNAGITPPGPLEELTEEDWDRVLDVNLKGPFLLTRAALPHM-RE 131

                          90       100       110
                  ....*....|....*....|....*....|...
gi 1895054273  81 DRGGVVIYMGSVHSHEASPLKSAYVTAKHGLLG 113
Cdd:COG1028   132 RGGGRIVNISSIAGLRGSPGQAAYAASKAAVVG 164

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1895054273   2 GGKAIGVAMDVTNEDAVNAGIDKVAAEFGSVDILVSNAGIQIVNPIENYSFSDWKKMQAIHVDGAFLTTKAALKHMyKDD 81
Cdd:COG4221    50 GGRALAVPLDVTDEAAVEAAVAAAVAEFGRLDVLVNNAGVALLGPLEELDPEDWDRMIDVNVKGVLYVTRAALPAM-RAR 128

                          90       100       110
                  ....*....|....*....|....*....|..
gi 1895054273  82 RGGVVIYMGSVHSHEASPLKSAYVTAKHGLLG 113
Cdd:COG4221   129 GSGHIVNISSIAGLRPYPGGAVYAATKAAVRG 160

bifunctional aldolase/short-chain dehydrogenase;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1895054273   1 AGGKAIGVAMDVTNEDAVNAGIDKVAAEFGSVDILVSNAGIQIVNPIENYSFSDWKKMQAIHVDGAFLTTKAALKHMYKD 80
Cdd:PRK08324  468 GPDRALGVACDVTDEAAVQAAFEEAALAFGGVDIVVSNAGIAISGPIEETSDEDWRRSFDVNATGHFLVAREAVRIMKAQ 547

                          90       100
                  ....*....|....*....|....*...
gi 1895054273  81 DRGGVVIYMGSVHSHEASPLKSAYVTAK 108
Cdd:PRK08324  548 GLGGSIVFIASKNAVNPGPNFGAYGAAK 575

d-3-hydroxybutyrate dehydrogenase (HBDH), classical (c) SDRs; DHBDH, an NAD+ -dependent enzyme, catalyzes the interconversion of D-3-hydroxybutyrate and acetoacetate. It is a classical SDR, with the canonical NAD-binding motif and active site tetrad. 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 1895054273   2 GGKAIGVAMDVTNEDAVNAGIDKVAAEFGSVDILVSNAGIQIVNPIENYSFSDWKKMQAIHVDGAFLTTKAALKHMYKDD 81
Cdd:cd08940    52 GVKVLYHGADLSKPAAIEDMVAYAQRQFGGVDILVNNAGIQHVAPIEDFPTEKWDAIIALNLSAVFHTTRLALPHMKKQG 131

                          90       100       110
                  ....*....|....*....|....*....|..
gi 1895054273  82 RGGvVIYMGSVHSHEASPLKSAYVTAKHGLLG 113
Cdd:cd08940   132 WGR-IINIASVHGLVASANKSAYVAAKHGVVG 162

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1895054273   1 AGGKAIGVAMDVTNEDAVNAGIDKVAAEFGSVDILVSNAGIQIVNPIENYSFSDWKKMQAIHVDGAFLTTKAALKHMYKd 80
Cdd:PRK05557   53 LGGKALAVQGDVSDAESVERAVDEAKAEFGGVDILVNNAGITRDNLLMRMKEEDWDRVIDTNLTGVFNLTKAVARPMMK- 131

                          90       100       110
                  ....*....|....*....|....*....|...
gi 1895054273  81 DRGGVVIYMGSVHSHEASPLKSAYVTAKHGLLG 113
Cdd:PRK05557  132 QRSGRIINISSVVGLMGNPGQANYAASKAGVIG 164

gluconate 5-dehydrogenase (Ga5DH)-like, classical (c) SDRs; Ga5DH catalyzes the NADP-dependent conversion of carbon source D-gluconate and 5-keto-D-gluconate. This SDR subgroup has a classical Gly-rich NAD(P)-binding motif and a conserved active site tetrad pattern. However, it has been proposed that Arg104 (Streptococcus suis Ga5DH numbering), as well as an active site Ca2+, play a critical role in catalysis. In addition to Ga5DHs this subgroup contains Erwinia chrysanthemi KduD which is involved in pectin degradation, and is a putative 2,5-diketo-3-deoxygluconate dehydrogenase. SDRs are a functionally diverse family of oxidoreductases that have a single domain with a structurally conserved Rossmann fold (alpha/beta folding pattern with a central beta-sheet), an NAD(P)(H)-binding region, and a structurally diverse C-terminal region. Classical SDRs are typically about 250 residues long, while extended SDRs are approximately 350 residues. Sequence identity between different SDR enzymes are typically in the 15-30% range, but the enzymes share the Rossmann fold NAD-binding motif and characteristic NAD-binding and catalytic sequence patterns. These enzymes catalyze a wide range of activities including the metabolism of steroids, cofactors, carbohydrates, lipids, aromatic compounds, and amino acids, and act in redox sensing. Classical SDRs have an TGXXX[AG]XG cofactor binding motif and a YXXXK active site motif, with the Tyr residue of the active site motif serving as a critical catalytic residue (Tyr-151, human 15-hydroxyprostaglandin dehydrogenase (15-PGDH) numbering). In addition to the Tyr and Lys, there is often an upstream Ser (Ser-138, 15-PGDH numbering) and/or an Asn (Asn-107,15-PGDH numbering) contributing to the active site; while substrate binding is in the C-terminal region, which determines specificity. The standard reaction mechanism is a 4-pro-S hydride transfer and proton relay involving the conserved Tyr and Lys, a water molecule stabilized by Asn, and nicotinamide. Extended SDRs have additional elements in the C-terminal region, and typically have a TGXXGXXG cofactor binding motif. Complex (multidomain) SDRs such as ketoreductase domains of fatty acid synthase have a GGXGXXG NAD(P)-binding motif and an altered active site motif (YXXXN). Fungal type ketoacyl reductases have a TGXXXGX(1-2)G NAD(P)-binding motif. Some atypical SDRs have lost catalytic activity and/or have an unusual NAD(P)-binding motif and missing or unusual active site residues. Reactions catalyzed within the SDR family include isomerization, decarboxylation, epimerization, C=N bond reduction, dehydratase activity, dehalogenation, Enoyl-CoA reduction, and carbonyl-alcohol oxidoreduction.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1895054273   1 AGGKAIGVAMDVTNEDAVNAGIDKVAAEFGSVDILVSNAGIQIVNPIENYSFSDWKKMQAIHVDGAFLTTKAALKHMYKD 80
Cdd:cd05347    52 EGVEATAFTCDVSDEEAIKAAVEAIEEDFGKIDILVNNAGIIRRHPAEEFPEAEWRDVIDVNLNGVFFVSQAVARHMIKQ 131

                          90       100       110
                  ....*....|....*....|....*....|...
gi 1895054273  81 DRGGvVIYMGSVHSHEASPLKSAYVTAKHGLLG 113
Cdd:cd05347   132 GHGK-IINICSLLSELGGPPVPAYAASKGGVAG 163

rhamnulose-1-phosphate aldolase/alcohol dehydrogenase, classical (c) SDRs; This family has bifunctional proteins with an N-terminal aldolase and a C-terminal classical SDR domain. One member is identified as a rhamnulose-1-phosphate aldolase/alcohol dehydrogenase. The SDR domain has a canonical SDR glycine-rich NAD(P) binding motif and a match to the characteristic active site triad. However, it lacks an upstream active site Asn typical of 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 1895054273   2 GGKAIGVAMDVTNEDAVNAGIDKVAAEFGSVDILVSNAGIQIVNPIENYSFSDWKKMQAIHVDGAFLTTKAALKHMYKDD 81
Cdd:cd08943    48 GPRALGVQCDVTSEAQVQSAFEQAVLEFGGLDIVVSNAGIATSSPIAETSLEDWNRSMDINLTGHFLVSREAFRIMKSQG 127

                          90       100       110
                  ....*....|....*....|....*....|.
gi 1895054273  82 RGGVVIYMGSVHSHEASPLKSAYVTAKHGLL 112
Cdd:cd08943   128 IGGNIVFNASKNAVAPGPNAAAYSAAKAAEA 158

glucose-1-dehydrogenase; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1895054273   1 AGGKAIGVAMDVTNEDAVNAGIDKVAAEFGSVDILVSNAGIQIVNPIENYSFSDWKKMQAIHVDGAFLTTKAALKHMYKD 80
Cdd:PRK08936   55 AGGEAIAVKGDVTVESDVVNLIQTAVKEFGTLDVMINNAGIENAVPSHEMSLEDWNKVINTNLTGAFLGSREAIKYFVEH 134

                          90       100       110
                  ....*....|....*....|....*....|.
gi 1895054273  81 DRGGVVIYMGSVHSHEASPLKSAYVTAKHGL 111
Cdd:PRK08936  135 DIKGNIINMSSVHEQIPWPLFVHYAASKGGV 165

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1895054273   1 AGGKAIGVAMDVTNEDAVNAGIDKVAAEFGSVDILVSNAGIQIVNPIENYSFSDWKKMQAIHVDGAFLTTKAALKHMYKd 80
Cdd:cd05333    47 LGGNAAALEADVSDREAVEALVEKVEAEFGPVDILVNNAGITRDNLLMRMSEEDWDAVINVNLTGVFNVTQAVIRAMIK- 125

                          90       100       110
                  ....*....|....*....|....*....|...
gi 1895054273  81 DRGGVVIYMGSVHSHEASPLKSAYVTAKHGLLG 113
Cdd:cd05333   126 RRSGRIINISSVVGLIGNPGQANYAASKAGVIG 158

SDR family oxidoreductase;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1895054273   1 AGGKAIGVAMDVTNEDAVNAGIDKVAAEFGSVDILVSNAGIQIVNPIENYSFSDWKKMQAIHVDGAFLTTKAALKHMyKD 80
Cdd:PRK12826   53 AGGKARARQVDVRDRAALKAAVAAGVEDFGRLDILVANAGIFPLTPFAEMDDEQWERVIDVNLTGTFLLTQAALPAL-IR 131

                          90       100       110
                  ....*....|....*....|....*....|....
gi 1895054273  81 DRGGVVIYMGSVH-SHEASPLKSAYVTAKHGLLG 113
Cdd:PRK12826  132 AGGGRIVLTSSVAgPRVGYPGLAHYAASKAGLVG 165

SDR family oxidoreductase;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1895054273   1 AGGKAIGVAMDVTNEDAVNAGIDKVAAEFGSVDILVSNAGIQIVN-PIENYSFSDWKKMQAIHVDGAFLTTKAALKHMyK 79
Cdd:PRK07231   51 AGGRAIAVAADVSDEADVEAAVAAALERFGSVDILVNNAGTTHRNgPLLDVDEAEFDRIFAVNVKSPYLWTQAAVPAM-R 129

                          90       100
                  ....*....|....*....|....*....
gi 1895054273  80 DDRGGVVIYMGSVHSHEASPLKSAYVTAK 108
Cdd:PRK07231  130 GEGGGAIVNVASTAGLRPRPGLGWYNASK 158

L-iditol 2-dehydrogenase;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1895054273   2 GGKAIGVAMDVTNEDAVNAGIDKVAAEFGSVDILVSNAGIQIVNPIENYSFSDWKKMQAIHVDGAFLTTKAALKHMYKDD 81
Cdd:PRK07067   51 GPAAIAVSLDVTRQDSIDRIVAAAVERFGGIDILFNNAALFDMAPILDISRDSYDRLFAVNVKGLFFLMQAVARHMVEQG 130

                          90       100
                  ....*....|....*....|....*..
gi 1895054273  82 RGGVVIYMGSVHSHEASPLKSAYVTAK 108
Cdd:PRK07067  131 RGGKIINMASQAGRRGEALVSHYCATK 157

meso-2,3-butanediol dehydrogenase-like, classical (c) SDRs; 2,3-butanediol dehydrogenases (BDHs) catalyze the NAD+ dependent conversion of 2,3-butanediol to acetonin; BDHs are classified into types according to their stereospecificity as to substrates and products. Included in this subgroup are Klebsiella pneumonia meso-BDH which catalyzes meso-2,3-butanediol to D(-)-acetonin, and Corynebacterium glutamicum L-BDH which catalyzes lX+)-2,3-butanediol to L(+)-acetonin. This subgroup is comprised of classical SDRs with the characteristic catalytic triad and 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 1895054273   1 AGGKAIGVAMDVTNEDAVNAGIDKVAAEFGSVDILVSNAGIQIVNPIENYSFSDWKKMQAIHVDGAFLTTKAALKHMYKD 80
Cdd:cd05366    50 AGYNAVAVGADVTDKDDVEALIDQAVEKFGSFDVMVNNAGIAPITPLLTITEEDLKKVYAVNVFGVLFGIQAAARQFKKL 129

                          90       100       110
                  ....*....|....*....|....*....|...
gi 1895054273  81 DRGGVVIYMGSVHSHEASPLKSAYVTAKHGLLG 113
Cdd:cd05366   130 GHGGKIINASSIAGVQGFPNLGAYSASKFAVRG 162

SDR family oxidoreductase;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1895054273   1 AGGKAIGVAMDVTNEDAVNAGIDKVAAEFGSVDILVSNAGIQIVNPIENYSFSDWKKMQAIHVDGAFLTTKAALKHMYKd 80
Cdd:PRK07326   52 NKGNVLGLAADVRDEADVQRAVDAIVAAFGGLDVLIANAGVGHFAPVEELTPEEWRLVIDTNLTGAFYTIKAAVPALKR- 130

                          90       100       110
                  ....*....|....*....|....*....|...
gi 1895054273  81 dRGGVVIYMGSVHSHEASPLKSAYVTAKHGLLG 113
Cdd:PRK07326  131 -GGGYIINISSLAGTNFFAGGAAYNASKFGLVG 162

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1895054273   5 AIGVAMDVTNEDAVNAGIDKVAAEFGSVDILVSNAGIQIVNPIENYSFSDWKKMQAIHVDGAFLTTKAALKHMYKdDRGG 84
Cdd:cd05374    48 LEVLELDVTDEESIKAAVKEVIERFGRIDVLVNNAGYGLFGPLEETSIEEVRELFEVNVFGPLRVTRAFLPLMRK-QGSG 126

                          90       100
                  ....*....|....*....|....*....
gi 1895054273  85 VVIYMGSVHSHEASPLKSAYVTAKHGLLG 113
Cdd:cd05374   127 RIVNVSSVAGLVPTPFLGPYCASKAALEA 155

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 1895054273   2 GGKAIGVAMDVTNEDAVNAGIDKVAAEFGSVDILVSNAGIQIVNPIENYSFSDWKKMQAIHVDGAFLTTKAALKHMyKDD 81
Cdd:cd05341    50 GDAARFFHLDVTDEDGWTAVVDTAREAFGRLDVLVNNAGILTGGTVETTTLEEWRRLLDINLTGVFLGTRAVIPPM-KEA 128

                          90       100       110
                  ....*....|....*....|....*....|..
gi 1895054273  82 RGGVVIYMGSVHSHEASPLKSAYVTAKHGLLG 113
Cdd:cd05341   129 GGGSIINMSSIEGLVGDPALAAYNASKGAVRG 160

Trans-2-enoyl-CoA reductase (TER) and 2,4-dienoyl-CoA reductase (DECR), atypical (a) SDR; TTER is a peroxisomal protein with a proposed role in fatty acid elongation. Fatty acid synthesis is known to occur in the both endoplasmic reticulum and mitochondria; peroxisomal TER has been proposed as an additional fatty acid elongation system, it reduces the double bond at C-2 as the last step of elongation. This system resembles the mitochondrial system in that acetyl-CoA is used as a carbon donor. TER may also function in phytol metabolism, reducting phytenoyl-CoA to phytanoyl-CoA in peroxisomes. DECR processes double bonds in fatty acids to increase their utility in fatty acid metabolism; it reduces 2,4-dienoyl-CoA to an enoyl-CoA. DECR is active in mitochondria and peroxisomes. This subgroup has the Gly-rich NAD-binding motif of the classical SDR family, but does not display strong identity to the canonical active site tetrad, and lacks the characteristic Tyr at the usual position. SDRs are a functionally diverse family of oxidoreductases that have a single domain with a structurally conserved Rossmann fold (alpha/beta folding pattern with a central beta-sheet), an NAD(P)(H)-binding region, and a structurally diverse C-terminal region. Classical SDRs are typically about 250 residues long, while extended SDRS are approximately 350 residues. Sequence identity between different SDR enzymes are typically in the 15-30% range, but the enzymes share the Rossmann fold NAD-binding motif and characteristic NAD-binding and catalytic sequence patterns. These enzymes have a 3-glycine N-terminal NAD(P)(H)-binding pattern (typically, TGxxxGxG in classical SDRs and TGxxGxxG in extended SDRs), while substrate binding is in the C-terminal region. A critical catalytic Tyr residue (Tyr-151, human 15-hydroxyprostaglandin dehydrogenase (15-PGDH) numbering), is often found in a conserved YXXXK pattern. In addition to the Tyr and Lys, there is often an upstream Ser (Ser-138, 15-PGDH numbering) and/or an Asn (Asn-107, 15-PGDH numbering) or additional Ser, contributing to the active site. Substrates for these enzymes include sugars, steroids, alcohols, and aromatic compounds. The standard reaction mechanism is a proton relay involving the conserved Tyr and Lys, as well as Asn (or Ser). Some SDR family members, including 17 beta-hydroxysteroid dehydrogenase contain an additional helix-turn-helix motif that is not generally found among SDRs.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1895054273   2 GGKAIGVAMDVTNEDAVNAGIDKVAAEFGSVDILVSNAGIQIVNPIENYSFSDWKKMQAIHVDGAFLTTKAALKHMYKDD 81
Cdd:cd05369    52 GGRAHPIQCDVRDPEAVEAAVDETLKEFGKIDILINNAAGNFLAPAESLSPNGFKTVIDIDLNGTFNTTKAVGKRLIEAK 131

                          90       100       110
                  ....*....|....*....|....*....|.
gi 1895054273  82 RGGVVIYMGSVHSHEASPLKSAYVTAKHGLL 112
Cdd:cd05369   132 HGGSILNISATYAYTGSPFQVHSAAAKAGVD 162

gluconate 5-dehydrogenase; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1895054273   1 AGGKAIGVAMDVTNEDAVNAGIDKVAAEFGSVDILVSNAGIQIVNPIENYSFSDWKKMQAIHVDGAFLTTKAALKHMYKd 80
Cdd:PRK07097   57 LGIEAHGYVCDVTDEDGVQAMVSQIEKEVGVIDILVNNAGIIKRIPMLEMSAEDFRQVIDIDLNAPFIVSKAVIPSMIK- 135

                          90       100       110
                  ....*....|....*....|....*....|.
gi 1895054273  81 DRGGVVIYMGSVHSHEASPLKSAYVTAKHGL 111
Cdd:PRK07097  136 KGHGKIINICSMMSELGRETVSAYAAAKGGL 166

short chain dehydrogenase; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1895054273   1 AGGKAIGVAMDVTNEDAVNAGIDKVAAEFGSVDILVSNAGIQIVNPIENYSFSDWKKMQAIHVDGAFLTTKAALKHMyKD 80
Cdd:PRK12939   54 AGGRAHAIAADLADPASVQRFFDAAAAALGGLDGLVNNAGITNSKSATELDIDTWDAVMNVNVRGTFLMLRAALPHL-RD 132

                          90       100       110
                  ....*....|....*....|....*....|...
gi 1895054273  81 DRGGVVIYMGSVHSHEASPLKSAYVTAKHGLLG 113
Cdd:PRK12939  133 SGRGRIVNLASDTALWGAPKLGAYVASKGAVIG 165

short chain dehydrogenase; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1895054273   1 AGGKAIGVAMDVTNEDAVNAGIDKVAAEFGSVDILVSNAGIQIVN-PIENYSFSDWKKMQAIHVDGAFLTTKAALKHMYK 79
Cdd:PRK12829   56 PGAKVTATVADVADPAQVERVFDTAVERFGGLDVLVNNAGIAGPTgGIDEITPEQWEQTLAVNLNGQFYFARAAVPLLKA 135

                          90       100       110
                  ....*....|....*....|....*....|....
gi 1895054273  80 DDRGGVVIYMGSVHSHEASPLKSAYVTAKHGLLG 113
Cdd:PRK12829  136 SGHGGVIIALSSVAGRLGYPGRTPYAASKWAVVG 169

tetrahydroxynaphthalene/trihydroxynaphthalene reductase-like, classical (c) SDRs; 1,3,6,8-tetrahydroxynaphthalene reductase (4HNR) of Magnaporthe grisea and the related 1,3,8-trihydroxynaphthalene reductase (3HNR) are typical members of the SDR family containing the canonical glycine rich NAD(P)-binding site and active site tetrad, and function in fungal melanin biosynthesis. This subgroup also includes an SDR from Norway spruce that may function to protect against both biotic and abitoic stress. SDRs are a functionally diverse family of oxidoreductases that have a single domain with a structurally conserved Rossmann fold (alpha/beta folding pattern with a central beta-sheet), an NAD(P)(H)-binding region, and a structurally diverse C-terminal region. Classical SDRs are typically about 250 residues long, while extended SDRs are approximately 350 residues. Sequence identity between different SDR enzymes are typically in the 15-30% range, but the enzymes share the Rossmann fold NAD-binding motif and characteristic NAD-binding and catalytic sequence patterns. These enzymes catalyze a wide range of activities including the metabolism of steroids, cofactors, carbohydrates, lipids, aromatic compounds, and amino acids, and act in redox sensing. Classical SDRs have an TGXXX[AG]XG cofactor binding motif and a YXXXK active site motif, with the Tyr residue of the active site motif serving as a critical catalytic residue (Tyr-151, human 15-hydroxyprostaglandin dehydrogenase (15-PGDH) numbering). In addition to the Tyr and Lys, there is often an upstream Ser (Ser-138, 15-PGDH numbering) and/or an Asn (Asn-107, 15-PGDH numbering) contributing to the active site; while substrate binding is in the C-terminal region, which determines specificity. The standard reaction mechanism is a 4-pro-S hydride transfer and proton relay involving the conserved Tyr and Lys, a water molecule stabilized by Asn, and nicotinamide. Extended SDRs have additional elements in the C-terminal region, and typically have a TGXXGXXG cofactor binding motif. Complex (multidomain) SDRs such as ketoreductase domains of fatty acid synthase have a GGXGXXG NAD(P)-binding motif and an altered active site motif (YXXXN). Fungal type ketoacyl reductases have a TGXXXGX(1-2)G NAD(P)-binding motif. Some atypical SDRs have lost catalytic activity and/or have an unusual NAD(P)-binding motif and missing or unusual active site residues. Reactions catalyzed within the SDR family include isomerization, decarboxylation, epimerization, C=N bond reduction, dehydratase activity, dehalogenation, Enoyl-CoA reduction, and carbonyl-alcohol oxidoreduction.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1895054273   1 AGGKAIGVAMDVTNEDAVNAGIDKVAAEFGSVDILVSNAGIQIVNPIENYSFSDWKKMQAIHVDGAFLTTKAALKHMykd 80
Cdd:cd05362    51 AGGKAIAVQADVSDPSQVARLFDAAEKAFGGVDILVNNAGVMLKKPIAETSEEEFDRMFTVNTKGAFFVLQEAAKRL--- 127

                          90       100
                  ....*....|....*....|....*...
gi 1895054273  81 DRGGVVIYMGSVHSHEASPLKSAYVTAK 108
Cdd:cd05362   128 RDGGRIINISSSLTAAYTPNYGAYAGSK 155

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 1895054273  11 DVTNEDAVNAGIDKVAAEFGSVDILVSNAGIQIVNPIENYSFSDWKKMQAIHVDGAFLTTKAALKHMYKDDRGGVVIyMG 90
Cdd:cd05352    66 DVSSQESVEKTFKQIQKDFGKIDILIANAGITVHKPALDYTYEQWNKVIDVNLNGVFNCAQAAAKIFKKQGKGSLII-TA 144

                          90       100
                  ....*....|....*....|..
gi 1895054273  91 SVHSHEAS-PLKSA-YVTAKHG 110
Cdd:cd05352   145 SMSGTIVNrPQPQAaYNASKAA 166

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1895054273   2 GGKAIGVAMDVTNEDAVNAGIDKVAAEFGSVDILVSNAGIQIVNPIENYSFSDWKKMQAIHVDGAFLTTKAALKHMyKDD 81
Cdd:PRK07666   55 GVKVVIATADVSDYEEVTAAIEQLKNELGSIDILINNAGISKFGKFLELDPAEWEKIIQVNLMGVYYATRAVLPSM-IER 133

                          90       100       110
                  ....*....|....*....|....*....|..
gi 1895054273  82 RGGVVIYMGSVHSHEASPLKSAYVTAKHGLLG 113
Cdd:PRK07666  134 QSGDIINISSTAGQKGAAVTSAYSASKFGVLG 165

SDR family oxidoreductase;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1895054273   1 AGGKAIGVAMDVTNEDAVNAGIDKVAAEFGSVDILVSNAGIQIVNPIENYSFSDWKKMQAIHVDGAFLTTKAALKHMYKd 80
Cdd:PRK06138   51 AGGRAFARQGDVGSAEAVEALVDFVAARWGRLDVLVNNAGFGCGGTVVTTDEADWDAVMRVNVGGVFLWAKYAIPIMQR- 129

                          90       100       110
                  ....*....|....*....|....*....|..
gi 1895054273  81 DRGGVVIYMGSVHSHEASPLKSAYVTAKHGLL 112
Cdd:PRK06138  130 QGGGSIVNTASQLALAGGRGRAAYVASKGAIA 161

insect type alcohol dehydrogenase (ADH)-like, classical (c) SDRs; This subgroup contains insect type ADH, and 15-hydroxyprostaglandin dehydrogenase (15-PGDH) type I; these proteins are classical SDRs. ADH catalyzes the NAD+-dependent oxidation of alcohols to aldehydes/ketones. This subgroup is distinct from the zinc-dependent alcohol dehydrogenases of the medium chain dehydrogenase/reductase family, and evolved in fruit flies to allow the digestion of fermenting fruit. 15-PGDH catalyzes the NAD-dependent interconversion of (5Z,13E)-(15S)-11alpha,15-dihydroxy-9-oxoprost-13-enoate and (5Z,13E)-11alpha-hydroxy-9,15-dioxoprost-13-enoate, and has a typical SDR glycine-rich NAD-binding motif, which is not fully present in ADH. SDRs are a functionally diverse family of oxidoreductases that have a single domain with a structurally conserved Rossmann fold (alpha/beta folding pattern with a central beta-sheet), an NAD(P)(H)-binding region, and a structurally diverse C-terminal region. Classical SDRs are typically about 250 residues long, while extended SDRs are approximately 350 residues. Sequence identity between different SDR enzymes are typically in the 15-30% range, but the enzymes share the Rossmann fold NAD-binding motif and characteristic NAD-binding and catalytic sequence patterns. These enzymes catalyze a wide range of activities including the metabolism of steroids, cofactors, carbohydrates, lipids, aromatic compounds, and amino acids, and act in redox sensing. Classical SDRs have an TGXXX[AG]XG cofactor binding motif and a YXXXK active site motif, with the Tyr residue of the active site motif serving as a critical catalytic residue (Tyr-151, human 15-hydroxyprostaglandin dehydrogenase (15-PGDH) numbering). In addition to the Tyr and Lys, there is often an upstream Ser (Ser-138, 15-PGDH numbering) and/or an Asn (Asn-107, 15-PGDH numbering) contributing to the active site; while substrate binding is in the C-terminal region, which determines specificity. The standard reaction mechanism is a 4-pro-S hydride transfer and proton relay involving the conserved Tyr and Lys, a water molecule stabilized by Asn, and nicotinamide. Extended SDRs have additional elements in the C-terminal region, and typically have a TGXXGXXG cofactor binding motif. Complex (multidomain) SDRs such as ketoreductase domains of fatty acid synthase have a GGXGXXG NAD(P)-binding motif and an altered active site motif (YXXXN). Fungal type ketoacyl reductases have a TGXXXGX(1-2)G NAD(P)-binding motif. Some atypical SDRs have lost catalytic activity and/or have an unusual NAD(P)-binding motif and missing or unusual active site residues. Reactions catalyzed within the SDR family include isomerization, decarboxylation, epimerization, C=N bond reduction, dehydratase activity, dehalogenation, Enoyl-CoA reduction, and carbonyl-alcohol oxidoreduction.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1895054273   2 GGKAIGVAMDVTNEDAVNAGIDKVAAEFGSVDILVSNAGIqivNPIENYSFS-----DWKKMQAIHVDGAFLTTKAALKH 76
Cdd:cd05323    48 KVKATFVQCDVTSWEQLAAAFKKAIEKFGRVDILINNAGI---LDEKSYLFAgklppPWEKTIDVNLTGVINTTYLALHY 124

                          90       100       110
                  ....*....|....*....|....*....|....*....
gi 1895054273  77 MYKDD--RGGVVIYMGSVHSHEASPLKSAYVTAKHGLLG 113
Cdd:cd05323   125 MDKNKggKGGVIVNIGSVAGLYPAPQFPVYSASKHGVVG 163