Rossmann-fold NAD(P)(+)-binding proteins; A large family of proteins that share a Rossmann-fold NAD(P)H/NAD(P)(+) binding (NADB) domain. The NADB domain is found in numerous dehydrogenases of metabolic pathways such as glycolysis, and many other redox enzymes. NAD binding involves numerous hydrogen-bonds and van der Waals contacts, in particular H-bonding of residues in a turn between the first strand and the subsequent helix of the Rossmann-fold topology. Characteristically, this turn exhibits a consensus binding pattern similar to GXGXXG, in which the first 2 glycines participate in NAD(P)-binding, and the third facilitates close packing of the helix to the beta-strand. Typically, proteins in this family contain a second domain in addition to the NADB domain, which is responsible for specifically binding a substrate and catalyzing a particular enzymatic reaction.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672717915   1 MMNVNTRGTYLTSKACIPFLKKSKVGHILNLSPPLNLNPLWFKQHCAYTIAKYGMSMCVLGMAEEFR-GEIAVNALWPRT 79
Cdd:cd09762  114 MMGVNTRGTYLCSKACLPYLKKSKNPHILNLSPPLNLNPKWFKNHTAYTMAKYGMSMCVLGMAEEFKpGGIAVNALWPRT 193

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|
gi 672717915  80 AIHTAAMDMLGGSGVENQCRKVDIIADAAYSIFKRPKS-FTGNFIIDENI 128
Cdd:cd09762  194 AIATAAMNMLGGVDVAACCRKPEIMADAAYAILTKPSSeFTGNFLIDEEV 243

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672717915   1 MMNVNTRGTYLTSKACIPFLKKSKVGHILNLSPPLNLNPLWFKQHCAYTIAKYGMSMCVLGMAEEFR-GEIAVNALWPRT 79
Cdd:cd09762  114 MMGVNTRGTYLCSKACLPYLKKSKNPHILNLSPPLNLNPKWFKNHTAYTMAKYGMSMCVLGMAEEFKpGGIAVNALWPRT 193

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|
gi 672717915  80 AIHTAAMDMLGGSGVENQCRKVDIIADAAYSIFKRPKS-FTGNFIIDENI 128
Cdd:cd09762  194 AIATAAMNMLGGVDVAACCRKPEIMADAAYAILTKPSSeFTGNFLIDEEV 243

SCP-2 sterol transfer family; This domain is involved in binding sterols. It is found in the SCP2 protein as well as the C terminus of the enzyme estradiol 17 beta-dehydrogenase EC:1.1.1.62. The UNC-24 protein contains an SPFH domain pfam01145.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672717915  270 KDSLSDEVVRATQA-VYQFELSGEdGGTWFLDLKSKGGKVGHGEPSDrADVVMSMATDDFVKMFSGKLKPTMAFMSGKLK 348
Cdd:pfam02036   7 RDPAARELLKKLNGkVIRFDLTDL-GLSLTLDLKDGGGRVLAGDEGK-ADVTLSASDSDLLALATGKLNPQKAFMQGKLK 84

                          90
                  ....*....|....*
gi 672717915  349 IKGNIALAIKLEKLM 363
Cdd:pfam02036  85 IEGDMELAQKLEGLL 99

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 672717915   1 MMNVNTRGTYLTSKACIPFLKKSKVGHILNLSPPLNLNPlwFKQHCAYTIAKYGMSMCVLGMAEEFRGE-IAVNALWPrT 79
Cdd:COG1028  110 VLDVNLKGPFLLTRAALPHMRERGGGRIVNISSIAGLRG--SPGQAAYAASKAAVVGLTRSLALELAPRgIRVNAVAP-G 186

                         90
                 ....*....|..
gi 672717915  80 AIHTAAMDMLGG 91
Cdd:COG1028  187 PIDTPMTRALLG 198

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672717915   1 MMNVNTRGTYLTSKACIPFLKKSKVGHILNLSPPLNLNPLWFKQHCAYTIAKYGMSMCVLGMAEEFR-GEIAVNALWPRT 79
Cdd:cd09762  114 MMGVNTRGTYLCSKACLPYLKKSKNPHILNLSPPLNLNPKWFKNHTAYTMAKYGMSMCVLGMAEEFKpGGIAVNALWPRT 193

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|
gi 672717915  80 AIHTAAMDMLGGSGVENQCRKVDIIADAAYSIFKRPKS-FTGNFIIDENI 128
Cdd:cd09762  194 AIATAAMNMLGGVDVAACCRKPEIMADAAYAILTKPSSeFTGNFLIDEEV 243

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672717915   1 MMNVNTRGTYLTSKACIPFLKKSKVGHILNLSPPLNLNPLWFkqHCAYTIAKYGMSMCVLGMAEEF-RGEIAVNALWPRT 79
Cdd:cd05338  119 MQRVNLRGTYLLSQAALPHMVKAGQGHILNISPPLSLRPARG--DVAYAAGKAGMSRLTLGLAAELrRHGIAVNSLWPST 196

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|
gi 672717915  80 AIHTAAMDMLGGSGVENQCRKVDIIADAAYSIFKRPK-SFTGNFIIDENI 128
Cdd:cd05338  197 AIETPAATELSGGSDPARARSPEILSDAVLAILSRPAaERTGLVVIDEEL 246

Putative sterol carrier protein, contains SCP2 domain [Lipid transport and metabolism];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672717915 283 AVYQFELSGEDGGTWFLDLKSKGGKVGHGEPSDrADVVMSMATDDFVKMFSGKLKPTMAFMSGKLKIKGNIALAIKLEKL 362
Cdd:COG3255   22 GVVQFVITGEGGGAYYLVIDDGKCTVSEGDDDD-ADVTLTASYEDWKKLLTGELDPMTAFMTGKLKVEGDMGLAMKLMSL 100

                 ....
gi 672717915 363 MTQM 366
Cdd:COG3255  101 FKAL 104

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 672717915   1 MMNVNTRGTYLTSKACIPFLKKSKVGHILNLSPPLNLNPlwFKQHCAYTIAKYGMSMCVLGMAEEFRGE-IAVNALWPrT 79
Cdd:COG1028  110 VLDVNLKGPFLLTRAALPHMRERGGGRIVNISSIAGLRG--SPGQAAYAASKAAVVGLTRSLALELAPRgIRVNAVAP-G 186

                         90
                 ....*....|..
gi 672717915  80 AIHTAAMDMLGG 91
Cdd:COG1028  187 PIDTPMTRALLG 198

Short-chain dehydrogenase [General function prediction only];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672717915   1 MMNVNTRGTYLTSKACIPFLKKSKVGHILNLSPPLNLNPLwfKQHCAYTIAKYGmsmcVLGMAEEFRGE-----IAVNAL 75
Cdd:COG0300  109 VFEVNVFGPVRLTRALLPLMRARGRGRIVNVSSVAGLRGL--PGMAAYAASKAA----LEGFSESLRAElaptgVRVTAV 182

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*
gi 672717915  76 WP---RTAIHTAAMDMLGGSGVEnqcrkVDIIADAAYSIFKRPKS 117
Cdd:COG0300  183 CPgpvDTPFTARAGAPAGRPLLS-----PEEVARAILRALERGRA 222

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

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 672717915    1 MMNVNTRGTYLTSKACIPFLKKSKVGHILNLSPPLNLNPlwFKQHCAYTIAKYGMSMCVLGMAEEFRG-EIAVNALWP 77
Cdd:pfam00106 104 VIDVNLTGVFNLTRAVLPAMIKGSGGRIVNISSVAGLVP--YPGGSAYSASKAAVIGFTRSLALELAPhGIRVNAVAP 179

glucose 1 dehydrogenase (GlcDH), classical (c) SDRs; GlcDH, is a tetrameric member of the SDR family, it catalyzes the NAD(P)-dependent oxidation of beta-D-glucose to D-glucono-delta-lactone. GlcDH has a typical NAD-binding site glycine-rich pattern as well as the canonical active site tetrad (YXXXK motif plus upstream Ser and Asn). 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 672717915   3 NVNTRGTYLTSKACIPFLKKSKV-GHILNLSPPLNLNPlWfKQHCAYTIAKYGMSMCVLGMAEEFRGE-IAVNALWP--- 77
Cdd:cd05358  110 DVNLTGQFLCAREAIKRFRKSKIkGKIINMSSVHEKIP-W-PGHVNYAASKGGVKMMTKTLAQEYAPKgIRVNAIAPgai 187

                         90
                 ....*....|
gi 672717915  78 RTAIHTAAMD 87
Cdd:cd05358  188 NTPINAEAWD 197

Enoyl-(Acyl carrier protein) reductase; This domain is found in Enoyl-(Acyl carrier protein) reductases.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672717915    1 MMNVNTRGTYLTSKACIPFLKKSkvGHILNLS--------PPLNlnplwfkqhcAYTIAKYGMSMCVLGMAEEFRGE-IA 71
Cdd:pfam13561 100 ALDVNLYSLFLLAKAALPLMKEG--GSIVNLSsigaervvPNYN----------AYGAAKAALEALTRYLAVELGPRgIR 167

                          90       100
                  ....*....|....*....|
gi 672717915   72 VNALWPrTAIHTAAMDMLGG 91
Cdd:pfam13561 168 VNAISP-GPIKTLAASGIPG 186

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672717915   1 MMNVNTRGTYLTSKACIPFLKKSKVGHILNLSPPLNLNPlwFKQHCAYTIAKYGmsmcVLGMAE----EFRGE-IAVNAL 75
Cdd:PRK07666 111 IIQVNLMGVYYATRAVLPSMIERQSGDIINISSTAGQKG--AAVTSAYSASKFG----VLGLTEslmqEVRKHnIRVTAL 184

                         90
                 ....*....|...
gi 672717915  76 WPRtaihTAAMDM 88
Cdd:PRK07666 185 TPS----TVATDM 193

pteridine reductase; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672717915   1 MMNVNTRGTYLTSKACIPFLKKSKvGHILNLSPPLNLNPLwfKQHCAYTIAKYGMSMCVLGMAEEFRGEIAVNA------ 74
Cdd:PRK09135 112 LFASNLKAPFFLSQAAAPQLRKQR-GAIVNITDIHAERPL--KGYPVYCAAKAALEMLTRSLALELAPEVRVNAvapgai 188

                 ...
gi 672717915  75 LWP 77
Cdd:PRK09135 189 LWP 191

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 672717915   1 MMNVNTRGTYLTSKACIPFLKKSKVGHILNLSPPLNLnpLWFKQHCAYTIAKYGMSMCVLGMAEEF-RGEIAVNALWP 77
Cdd:cd05347  109 VIDVNLNGVFFVSQAVARHMIKQGHGKIINICSLLSE--LGGPPVPAYAASKGGVAGLTKALATEWaRHGIQVNAIAP 184

human 17beta-hydroxysteroid dehydrogenase type 2 (type 2 17beta-HSD)-like, classical (c) SDRs; 17beta-hydroxysteroid dehydrogenases are a group of isozymes that catalyze activation and inactivation of estrogen and androgens. This classical-SDR subgroup includes the human proteins: type 2 17beta-HSD, type 6 17beta-HSD, type 2 11beta-HSD, dehydrogenase/reductase SDR family member 9, short-chain dehydrogenase/reductase family 9C member 7, 3-hydroxybutyrate dehydrogenase type 1, and retinol dehydrogenase 5. 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 672717915   1 MMNVNTRGTYLTSKACIPFLKKSKvGHILNLSPPLNLNPlwFKQHCAYTIAKYGMSM 57
Cdd:cd09805  106 CMEVNLFGTVEVTKAFLPLLRRAK-GRVVNVSSMGGRVP--FPAGGAYCASKAAVEA 159

SDR family oxidoreductase;

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672717915   1 MMNVNTRGTYLTSKACIPFLKKsKVGHILNLSP----PLNLNplwfkqHCAYTIAKYGMSMCVLGMAEEF-RGEIAVNAL 75
Cdd:PRK08589 110 IMAVDMRGTFLMTKMLLPLMME-QGGSIINTSSfsgqAADLY------RSGYNAAKGAVINFTKSIAIEYgRDGIRANAI 182

                         90
                 ....*....|....*..
gi 672717915  76 WPRTaIHTAAMDMLGGS 92
Cdd:PRK08589 183 APGT-IETPLVDKLTGT 198

short chain dehydrogenase; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672717915   1 MMNVNTRGTYLTSKACIPFLKKSK-VGHILNLS---PPLNLnPLWfkQHcaYTIAKYGMSMCVLGMAEEFRGE-IAVNAL 75
Cdd:PRK12829 114 TLAVNLNGQFYFARAAVPLLKASGhGGVIIALSsvaGRLGY-PGR--TP--YAASKWAVVGLVKSLAIELGPLgIRVNAI 188

                         90
                 ....*....|..
gi 672717915  76 WPrTAIHTAAMD 87
Cdd:PRK12829 189 LP-GIVRGPRMR 199

cis-biphenyl-2,3-dihydrodiol-2,3-dehydrogenase (BphB)-like, classical (c) SDRs; cis-biphenyl-2,3-dihydrodiol-2,3-dehydrogenase (BphB) is a classical SDR, it is of particular importance for its role in the degradation of biphenyl/polychlorinated biphenyls(PCBs); PCBs are a significant source of environmental contamination. This subgroup also includes Pseudomonas putida F1 cis-biphenyl-1,2-dihydrodiol-1,2-dehydrogenase (aka cis-benzene glycol dehydrogenase, encoded by the bnzE gene), which participates in benzene metabolism. In addition it includes Pseudomonas sp. C18 putative 1,2-dihydroxy-1,2-dihydronaphthalene dehydrogenase (aka dibenzothiophene dihydrodiol dehydrogenase, encoded by the doxE gene) which participates in an upper naphthalene catabolic 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, 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 672717915   1 MMNVNTRGTYLTSKACIPFLKKSKVGHILNLSP----PLNLNPLwfkqhcaYTIAKYGMSMCVLGMAEEFRGEIAVNALW 76
Cdd:cd05348  110 LFHINVKGYILGAKAALPALYATEGSVIFTVSNagfyPGGGGPL-------YTASKHAVVGLVKQLAYELAPHIRVNGVA 182

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....
gi 672717915  77 PrTAIHTaamDMLGGSGVENQCRKVDI--IADAAYSI-----FKRPKSFTGNFI 123
Cdd:cd05348  183 P-GGMVT---DLRGPASLGQGETSISTppLDDMLKSIlplgfAPEPEDYTGAYV 232

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        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672717915   1 MMNVNTRGTYLTSKACIPFLKKSKVGHILNLSPP---LNLNPLwfKQHCAYTIAKYGMSMCVLGMAEEFRGE-IAVNAL- 75
Cdd:cd05325  103 VFQVNVLGPLLLTQAFLPLLLKGARAKIINISSRvgsIGDNTS--GGWYSYRASKAALNMLTKSLAVELKRDgITVVSLh 180

                         90       100
                 ....*....|....*....|....
gi 672717915  76 --WPRTaihtaamDMLGGSGVENQ 97
Cdd:cd05325  181 pgWVRT-------DMGGPFAKNKG 197

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

                         10        20        30
                 ....*....|....*....|....*....|..
gi 672717915   1 MMNVNTRGTYLTSKACIPFLKKSKVGHILNLS 32
Cdd:PRK05565 110 VIDVNLTGVMLLTRYALPYMIKRKSGVIVNIS 141

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 672717915   1 MMNVNTRGTYLTSKACIPFLKKSKVGHILNLSPPLNLNPlwFKQHCAYTIAKYGmsmcVLGMAEEFRGEIA 71
Cdd:cd08939  109 GMDVNYFGSLNVAHAVLPLMKEQRPGHIVFVSSQAALVG--IYGYSAYCPSKFA----LRGLAESLRQELK 173

classical (c) SDR, subgroup 11; 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 672717915   2 MNVNTRGTYLTSKACIPFLKKSKvGHILNLS 32
Cdd:cd05364  111 MNLNLRAVIYLTKLAVPHLIKTK-GEIVNVS 140