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 530388794   1 MDVLKATAEQISSQTGNKVHAIQCDVRDPDMVQNTVSELIKVAGHPNIVINNAAGNFISPTERLSPNAWKTITDIVLNGT 80
Cdd:cd05369   37 PEVLEAAAEEISSATGGRAHPIQCDVRDPEAVEAAVDETLKEFGKIDILINNAAGNFLAPAESLSPNGFKTVIDIDLNGT 116

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530388794  81 AFVTLEIGKQLIKAQKGAAFLSITTIYAETGSGFVVPSASAKAGVEAMSKSLAAEWGKYGMRFNVIQPGPIKTKGAFSRL 160
Cdd:cd05369  117 FNTTKAVGKRLIEAKHGGSILNISATYAYTGSPFQVHSAAAKAGVDALTRSLAVEWGPYGIRVNAIAPGPIPTTEGMERL 196

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|.
gi 530388794 161 DPTGTFEKEMIGRIPCGRLGTVEELANLAAFLCSDYASWINGAVIKFDGGE 211
Cdd:cd05369  197 APSGKSEKKMIERVPLGRLGTPEEIANLALFLLSDAASYINGTTLVVDGGQ 247

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 530388794   1 MDVLKATAEQISSQTGNKVHAIQCDVRDPDMVQNTVSELIKVAGHPNIVINNAAGNFISPTERLSPNAWKTITDIVLNGT 80
Cdd:cd05369   37 PEVLEAAAEEISSATGGRAHPIQCDVRDPEAVEAAVDETLKEFGKIDILINNAAGNFLAPAESLSPNGFKTVIDIDLNGT 116

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530388794  81 AFVTLEIGKQLIKAQKGAAFLSITTIYAETGSGFVVPSASAKAGVEAMSKSLAAEWGKYGMRFNVIQPGPIKTKGAFSRL 160
Cdd:cd05369  117 FNTTKAVGKRLIEAKHGGSILNISATYAYTGSPFQVHSAAAKAGVDALTRSLAVEWGPYGIRVNAIAPGPIPTTEGMERL 196

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|.
gi 530388794 161 DPTGTFEKEMIGRIPCGRLGTVEELANLAAFLCSDYASWINGAVIKFDGGE 211
Cdd:cd05369  197 APSGKSEKKMIERVPLGRLGTPEEIANLALFLLSDAASYINGTTLVVDGGQ 247

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 530388794   2 DVLKATAEQISSQtGNKVHAIQCDVRDPDMVQNTVSELIKVAGHPNIVINNAAGNFISPTERLSPNAWKTITDIVLNGTA 81
Cdd:COG1028   41 EALEAAAAELRAA-GGRALAVAADVTDEAAVEALVAAAVAAFGRLDILVNNAGITPPGPLEELTEEDWDRVLDVNLKGPF 119

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530388794  82 FVTLEIGKQLiKAQKGAAFLSITTIYAETGSGFVVPSASAKAGVEAMSKSLAAEWGKYGMRFNVIQPGPIKTkGAFSRLD 161
Cdd:COG1028  120 LLTRAALPHM-RERGGGRIVNISSIAGLRGSPGQAAYAASKAAVVGLTRSLALELAPRGIRVNAVAPGPIDT-PMTRALL 197

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*....
gi 530388794 162 PTGTFEKEMIGRIPCGRLGTVEELANLAAFLCSDYASWINGAVIKFDGG 210
Cdd:COG1028  198 GAEEVREALAARIPLGRLGTPEEVAAAVLFLASDAASYITGQVLAVDGG 246

2-deoxy-D-gluconate 3-dehydrogenase; This model describes 2-deoxy-D-gluconate 3-dehydrogenase (also called 2-keto-3-deoxygluconate oxidoreductase), a member of the family of short-chain-alcohol dehydrogenases (pfam00106). This protein has been characterized in Erwinia chrysanthemi as an enzyme of pectin degradation. [Energy metabolism, Biosynthesis and degradation of polysaccharides]

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530388794    4 LKATAEQISsQTGNKVHAIQCDVRDPDMVQNTVSELIKVAGHPNIVINNAAGNFISPTERLSPNAWKTITDIVLNGTAFV 83
Cdd:TIGR01832  40 PSETQQQVE-ALGRRFLSLTADLSDIEAIKALVDSAVEEFGHIDILVNNAGIIRRADAEEFSEKDWDDVMNVNLKSVFFL 118

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530388794   84 TLEIGKQLIKAQKGAAFLSITTIYAETGsGFVVPSASA-KAGVEAMSKSLAAEWGKYGMRFNVIQPGPIKTKG-AFSRLD 161
Cdd:TIGR01832 119 TQAAAKHFLKQGRGGKIINIASMLSFQG-GIRVPSYTAsKHAVAGLTKLLANEWAAKGINVNAIAPGYMATNNtQALRAD 197

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*....
gi 530388794  162 PTGTfeKEMIGRIPCGRLGTVEELANLAAFLCSDYASWINGAVIKFDGG 210
Cdd:TIGR01832 198 EDRN--AAILERIPAGRWGTPDDIGGPAVFLASSASDYVNGYTLAVDGG 244

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 530388794   1 MDVLKATAEQISSQTGNKVHAIQCDVRDPDMVQNTVSELIKVAGHPNIVINNAAGNFISPTERLSPNAWKTITDIVLNGT 80
Cdd:cd05369   37 PEVLEAAAEEISSATGGRAHPIQCDVRDPEAVEAAVDETLKEFGKIDILINNAAGNFLAPAESLSPNGFKTVIDIDLNGT 116

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530388794  81 AFVTLEIGKQLIKAQKGAAFLSITTIYAETGSGFVVPSASAKAGVEAMSKSLAAEWGKYGMRFNVIQPGPIKTKGAFSRL 160
Cdd:cd05369  117 FNTTKAVGKRLIEAKHGGSILNISATYAYTGSPFQVHSAAAKAGVDALTRSLAVEWGPYGIRVNAIAPGPIPTTEGMERL 196

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|.
gi 530388794 161 DPTGTFEKEMIGRIPCGRLGTVEELANLAAFLCSDYASWINGAVIKFDGGE 211
Cdd:cd05369  197 APSGKSEKKMIERVPLGRLGTPEEIANLALFLLSDAASYINGTTLVVDGGQ 247

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 530388794   2 DVLKATAEQISSQtGNKVHAIQCDVRDPDMVQNTVSELIKVAGHPNIVINNAAGNFISPTERLSPNAWKTITDIVLNGTA 81
Cdd:COG1028   41 EALEAAAAELRAA-GGRALAVAADVTDEAAVEALVAAAVAAFGRLDILVNNAGITPPGPLEELTEEDWDRVLDVNLKGPF 119

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530388794  82 FVTLEIGKQLiKAQKGAAFLSITTIYAETGSGFVVPSASAKAGVEAMSKSLAAEWGKYGMRFNVIQPGPIKTkGAFSRLD 161
Cdd:COG1028  120 LLTRAALPHM-RERGGGRIVNISSIAGLRGSPGQAAYAASKAAVVGLTRSLALELAPRGIRVNAVAPGPIDT-PMTRALL 197

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*....
gi 530388794 162 PTGTFEKEMIGRIPCGRLGTVEELANLAAFLCSDYASWINGAVIKFDGG 210
Cdd:COG1028  198 GAEEVREALAARIPLGRLGTPEEVAAAVLFLASDAASYITGQVLAVDGG 246

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 530388794  16 GNKVHAIQCDVRDPDMVQNTVSELIKVAGHPNIVINNAAGNFISPTERLSPNAWKTITDIVLNGTAFVTLEIGKQLIKAQ 95
Cdd:cd05233   45 GGNAVAVQADVSDEEDVEALVEEALEEFGRLDILVNNAGIARPGPLEELTDEDWDRVLDVNLTGVFLLTRAALPHMKKQG 124

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530388794  96 KGAAFLsITTIYAETGSGFVVPSASAKAGVEAMSKSLAAEWGKYGMRFNVIQPGPIKTKGAFSRLDPTGtfEKEMIGRIP 175
Cdd:cd05233  125 GGRIVN-ISSVAGLRPLPGQAAYAASKAALEGLTRSLALELAPYGIRVNAVAPGLVDTPMLAKLGPEEA--EKELAAAIP 201

                        170       180       190
                 ....*....|....*....|....*....|...
gi 530388794 176 CGRLGTVEELANLAAFLCSDYASWINGAVIKFD 208
Cdd:cd05233  202 LGRLGTPEEVAEAVVFLASDEASYITGQVIPVD 234

short chain dehydrogenase; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530388794   6 ATAEQISsQTGNKVHAIQCDVRDPDMVQNTVSELIKVAGHPNIVINNAAGNFISPTERLSPNAWKTITDIVLNGTaFVTL 85
Cdd:PRK07576  48 AAVAQLQ-QAGPEGLGVSADVRDYAAVEAAFAQIADEFGPIDVLVSGAAGNFPAPAAGMSANGFKTVVDIDLLGT-FNVL 125

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530388794  86 EIGKQLIKaQKGAAFLSITTIYAETGSGFVVPSASAKAGVEAMSKSLAAEWGKYGMRFNVIQPGPIKTKGAFSRLDPTGT 165
Cdd:PRK07576 126 KAAYPLLR-RPGASIIQISAPQAFVPMPMQAHVCAAKAGVDMLTRTLALEWGPEGIRVNSIVPGPIAGTEGMARLAPSPE 204

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*
gi 530388794 166 FEKEMIGRIPCGRLGTVEELANLAAFLCSDYASWINGAVIKFDGG 210
Cdd:PRK07576 205 LQAAVAQSVPLKRNGTKQDIANAALFLASDMASYITGVVLPVDGG 249

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 530388794   7 TAEQISSQTGNKVHAIQCDVRDPDMVQNTVSELIKVAGHPNIVINNAAGNFISPTERLSPNAWKTITDIVLNGTAFVTLE 86
Cdd:cd05347   44 EAQQLIEKEGVEATAFTCDVSDEEAIKAAVEAIEEDFGKIDILVNNAGIIRRHPAEEFPEAEWRDVIDVNLNGVFFVSQA 123

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530388794  87 IGKQLIKaQKGAAFLSITTIYAETGSGFVVPSASAKAGVEAMSKSLAAEWGKYGMRFNVIQPGPIKTK-GAFSRLDPtgT 165
Cdd:cd05347  124 VARHMIK-QGHGKIINICSLLSELGGPPVPAYAASKGGVAGLTKALATEWARHGIQVNAIAPGYFATEmTEAVVADP--E 200

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*
gi 530388794 166 FEKEMIGRIPCGRLGTVEELANLAAFLCSDYASWINGAVIKFDGG 210
Cdd:cd05347  201 FNDDILKRIPAGRWGQPEDLVGAAVFLASDASDYVNGQIIFVDGG 245

putative beta-ketoacyl acyl carrier protein [ACP] reductase (BKR)-like, SDR; This subgroup resembles the SDR family, but does not have a perfect match to the NAD-binding motif or the catalytic tetrad characteristic of the SDRs. It includes the SDRs, Q9HYA2 from Pseudomonas aeruginosa PAO1 and APE0912 from Aeropyrum pernix K1. BKR catalyzes the NADPH-dependent reduction of ACP in the first reductive step of de novo fatty acid synthesis (FAS). FAS consists of four elongation steps, which are repeated to extend the fatty acid chain through the addition of two-carbo units from malonyl acyl-carrier protein (ACP): condensation, reduction, dehydration, and a final reduction. Type II FAS, typical of plants and many bacteria, maintains these activities on discrete polypeptides, while type I FAS utilizes one or two multifunctional polypeptides. BKR resembles enoyl reductase, which catalyzes the second reduction step in FAS. SDRs are a functionally diverse family of oxidoreductases that have a single domain with a structurally conserved Rossmann fold (alpha/beta folding pattern with a central beta-sheet), an NAD(P)(H)-binding region, and a structurally diverse C-terminal region. Classical SDRs are typically about 250 residues long, while extended SDRS are approximately 350 residues. Sequence identity between different SDR enzymes are typically in the 15-30% range, but the enzymes share the Rossmann fold NAD-binding motif and characteristic NAD-binding and catalytic sequence patterns. These enzymes have a 3-glycine N-terminal NAD(P)(H)-binding pattern (typically, TGxxxGxG in classical SDRs and TGxxGxxG in extended SDRs), while substrate binding is in the C-terminal region. A critical catalytic Tyr residue (Tyr-151, human 15-hydroxyprostaglandin dehydrogenase (15-PGDH) numbering), is often found in a conserved YXXXK pattern. In addition to the Tyr and Lys, there is often an upstream Ser (Ser-138, 15-PGDH numbering) and/or an Asn (Asn-107, 15-PGDH numbering) or additional Ser, contributing to the active site. Substrates for these enzymes include sugars, steroids, alcohols, and aromatic compounds. The standard reaction mechanism is a proton relay involving the conserved Tyr and Lys, as well as Asn (or Ser). Some SDR family members, including 17 beta-hydroxysteroid dehydrogenase contain an additional helix-turn-helix motif that is not generally found among SDRs.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530388794   2 DVLKATAEQISsQTGNKVHAIQCDVRDPDMVQNTVSELIKVAGHPNIVINNAAGNFISPTERLSPNAWKTITDIVLNGTA 81
Cdd:cd05344   36 ENLERAASELR-AGGAGVLAVVADLTDPEDIDRLVEKAGDAFGRVDILVNNAGGPPPGPFAELTDEDWLEAFDLKLLSVI 114

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530388794  82 FVTLEIGKQLIKaQKGAAFLSITTIYA-ETGSGFVVpSASAKAGVEAMSKSLAAEWGKYGMRFNVIQPGPIKT------- 153
Cdd:cd05344  115 RIVRAVLPGMKE-RGWGRIVNISSLTVkEPEPNLVL-SNVARAGLIGLVKTLSRELAPDGVTVNSVLPGYIDTervrrll 192

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 530388794 154 -KGAFSRLDPTGTFEKEMIGRIPCGRLGTVEELANLAAFLCSDYASWINGAVIKFDGG 210
Cdd:cd05344  193 eARAEKEGISVEEAEKEVASQIPLGRVGKPEELAALIAFLASEKASYITGQAILVDGG 250

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 530388794   5 KATAEQISSQTGNKVHAIQCDVRDPDMVQNTVSELIKVAGHPNIVINNA---AGNFIsptERLSPNAWKTITDIVLNGTA 81
Cdd:cd05333   37 AAETVEEIKALGGNAAALEADVSDREAVEALVEKVEAEFGPVDILVNNAgitRDNLL---MRMSEEDWDAVINVNLTGVF 113

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530388794  82 FVTLEIGKQLIKAQKGAaFLSITTIYAETGSGFVVPSASAKAGVEAMSKSLAAEWGKYGMRFNVIQPGPIKTkgafsrlD 161
Cdd:cd05333  114 NVTQAVIRAMIKRRSGR-IINISSVVGLIGNPGQANYAASKAGVIGFTKSLAKELASRGITVNAVAPGFIDT-------D 185

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|...
gi 530388794 162 PTGTFE----KEMIGRIPCGRLGTVEELANLAAFLCSDYASWINGAVIKFDGG 210
Cdd:cd05333  186 MTDALPekvkEKILKQIPLGRLGTPEEVANAVAFLASDDASYITGQVLHVNGG 238

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530388794   5 KATAEQISSQtGNKVHAIQCDVRDPDMVQNTVSELIKVAGHPNIVINNAAGNFISPTERLSPNAWKTITDIVLNGTAFVT 84
Cdd:PRK05565  44 QELLEEIKEE-GGDAIAVKADVSSEEDVENLVEQIVEKFGKIDILVNNAGISNFGLVTDMTDEEWDRVIDVNLTGVMLLT 122

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530388794  85 LEIGKQLIKaQKGAAFLSITTIYAETGSGFVVPSASAKAGVEAMSKSLAAEWGKYGMRFNVIQPGPIKTK-GAFSRLDpt 163
Cdd:PRK05565 123 RYALPYMIK-RKSGVIVNISSIWGLIGASCEVLYSASKGAVNAFTKALAKELAPSGIRVNAVAPGAIDTEmWSSFSEE-- 199

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*...
gi 530388794 164 gtfEKEMIGR-IPCGRLGTVEELANLAAFLCSDYASWINGAVIKFDGG 210
Cdd:PRK05565 200 ---DKEGLAEeIPLGRLGKPEEIAKVVLFLASDDASYITGQIITVDGG 244

gluconate 5-dehydrogenase; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530388794   4 LKATAEQISSqTGNKVHAIQCDVRDPDMVQNTVSELIKVAGHPNIVINNAAGNFISPTERLSPNAWKTITDIVLNGTAFV 83
Cdd:PRK08213  49 LEEAAAHLEA-LGIDALWIAADVADEADIERLAEETLERFGHVDILVNNAGATWGAPAEDHPVEAWDKVMNLNVRGLFLL 127

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530388794  84 TLEIGKQLIKAQKGAAFLSITTIYAETGS-----GFVVPSASaKAGVEAMSKSLAAEWGKYGMRFNVIQPG--PIK-TKG 155
Cdd:PRK08213 128 SQAVAKRSMIPRGYGRIINVASVAGLGGNppevmDTIAYNTS-KGAVINFTRALAAEWGPHGIRVNAIAPGffPTKmTRG 206

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 530388794 156 AFSRLdptgtfEKEMIGRIPCGRLGTVEELANLAAFLCSDYASWINGAVIKFDGG 210
Cdd:PRK08213 207 TLERL------GEDLLAHTPLGRLGDDEDLKGAALLLASDASKHITGQILAVDGG 255

1-cyclohexenylcarbonyl_coenzyme A_reductase (ChcA)_like, classical (c) SDRs; This subgroup contains classical SDR proteins, including members identified as 1-cyclohexenylcarbonyl coenzyme A reductase. ChcA of Streptomyces collinus is implicated in the final reduction step of shikimic acid to ansatrienin. ChcA shows sequence similarity to the SDR family of NAD-binding proteins, but it lacks the conserved Tyr of the characteristic catalytic site. This subgroup also contains the NADH-dependent enoyl-[acyl-carrier-protein(ACP)] reductase FabL from Bacillus subtilis. This enzyme participates in bacterial fatty acid synthesis, in type II fatty-acid synthases and catalyzes the last step in each elongation cycle. 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 530388794   5 KATAEQISSQtGNKVHAIQCDVRDPDMVQNTVSELIKVAGHPNIVINNAAGNFISPTERLSPNAWKTITDIVLNGTAFVT 84
Cdd:cd05359   37 AEVAAEIEEL-GGKAVVVRADVSQPQDVEEMFAAVKERFGRLDVLVSNAAAGAFRPLSELTPAHWDAKMNTNLKALVHCA 115

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530388794  85 LEIGKqLIKAQKGAAFLSITTiyaeTGSGFVVPS----ASAKAGVEAMSKSLAAEWGKYGMRFNVIQPGPIKTKGAFSRL 160
Cdd:cd05359  116 QQAAK-LMRERGGGRIVAISS----LGSIRALPNylavGTAKAALEALVRYLAVELGPRGIRVNAVSPGVIDTDALAHFP 190

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|
gi 530388794 161 DPTGTfEKEMIGRIPCGRLGTVEELANLAAFLCSDYASWINGAVIKFDGG 210
Cdd:cd05359  191 NREDL-LEAAAANTPAGRVGTPQDVADAVGFLCSDAARMITGQTLVVDGG 239

SDR family oxidoreductase;

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530388794   4 LKATAEQIssQTGNKVHAIQCDVRDPDMVQNTVSELIKVAGHPNIVINNAAGNFI-SPTERLSPNAWKTITDIVLNGTAF 82
Cdd:PRK07231  42 AERVAAEI--LAGGRAIAVAADVSDEADVEAAVAAALERFGSVDILVNNAGTTHRnGPLLDVDEAEFDRIFAVNVKSPYL 119

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530388794  83 VTLEIGKQLiKAQKGAAFLSITTIYAETGSGFVVPSASAKAGVEAMSKSLAAEWGKYGMRFNVIQPGPIKTKGAFSRL-D 161
Cdd:PRK07231 120 WTQAAVPAM-RGEGGGAIVNVASTAGLRPRPGLGWYNASKGAVITLTKALAAELGPDKIRVNAVAPVVVETGLLEAFMgE 198

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*....
gi 530388794 162 PTGTFEKEMIGRIPCGRLGTVEELANLAAFLCSDYASWINGAVIKFDGG 210
Cdd:PRK07231 199 PTPENRAKFLATIPLGRLGTPEDIANAALFLASDEASWITGVTLVVDGG 247

short chain dehydrogenase; Validated

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530388794   6 ATAEQISSQTGNKVHAIQCDVRDPDMVQNTVSELIKVAGHPNIVINNAA--GNFISPTERLSPNAWKTITDIVLNGTAFV 83
Cdd:PRK06484  40 ERARERADSLGPDHHALAMDVSDEAQIREGFEQLHREFGRIDVLVNNAGvtDPTMTATLDTTLEEFARLQAINLTGAYLV 119

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530388794  84 TLEIGKQLIKAQKGAAFLSITTIYAETGSGFVVPSASAKAGVEAMSKSLAAEWGKYGMRFNVIQPGPIKTKgAFSRLDPT 163
Cdd:PRK06484 120 AREALRLMIEQGHGAAIVNVASGAGLVALPKRTAYSASKAAVISLTRSLACEWAAKGIRVNAVLPGYVRTQ-MVAELERA 198

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*...
gi 530388794 164 GTFEKEMI-GRIPCGRLGTVEELANLAAFLCSDYASWINGAVIKFDGG 210
Cdd:PRK06484 199 GKLDPSAVrSRIPLGRLGRPEEIAEAVFFLASDQASYITGSTLVVDGG 246

short chain dehydrogenase; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530388794   4 LKATAEQISSQtGNKVHAIQCDVRDPDMVQNTVSELIKVAGHPNIVINNAAGNFISPTERLSPNAWKTITDIVLNGTAFV 83
Cdd:PRK12827  47 ADAVAAGIEAA-GGKALGLAFDVRDFAATRAALDAGVEEFGRLDILVNNAGIATDAAFAELSIEEWDDVIDVNLDGFFNV 125

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530388794  84 TLEIGKQLIKAQKGAAFLSITTIYAETGSGFVVPSASAKAGVEAMSKSLAAEWGKYGMRFNVIQPGPIKTKGAfSRLDPT 163
Cdd:PRK12827 126 TQAALPPMIRARRGGRIVNIASVAGVRGNRGQVNYAASKAGLIGLTKTLANELAPRGITVNAVAPGAINTPMA-DNAAPT 204

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*..
gi 530388794 164 GTFEKEMigriPCGRLGTVEELANLAAFLCSDYASWINGAVIKFDGG 210
Cdd:PRK12827 205 EHLLNPV----PVQRLGEPDEVAALVAFLVSDAASYVTGQVIPVDGG 247