short chain dehydrogenase; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958679612   1 MIMTMKGQVCVVTGASRGIGRGIALQLCQAGATVYITGRHL----------DTLRATAQEAQSLGGRCVPVVCDSSQESE 70
Cdd:PRK08303    2 MMKPLRGKVALVAGATRGAGRGIAVELGAAGATVYVTGRSTrarrseydrpETIEETAELVTAAGGRGIAVQVDHLVPEQ 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958679612  71 VKSLFEQVDREqQGRLDVLVNNAY------------------AGVQCDKLAADC-------------------------- 106
Cdd:PRK08303   82 VRALVERIDRE-QGRLDILVNDIWggeklfewgkpvwehsldKGLRMLRLAIDThlitshfalpllirrpgglvveitdg 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958679612 107 -----------------------------AHELRRHGVSYVSLWPGLVQTEMVKE-YVAKEEQPEDPLFKKMKSVLSsaE 156
Cdd:PRK08303  161 taeynathyrlsvfydlaktsvnrlafslAHELAPHGATAVALTPGWLRSEMMLDaFGVTEENWRDALAKEPHFAIS--E 238

                         250       260       270       280
                  ....*....|....*....|....*....|....*....|....*
gi 1958679612 157 TTEMSGKCVVALATDPNILSLSGKVLPSCDLARRYGLKDVDG-RP 200
Cdd:PRK08303  239 TPRYVGRAVAALAADPDVARWNGQSLSSGQLARVYGFTDLDGsRP 283

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958679612   8 QVCVVTGASRGIGRGIALQLCQAGATVYITGRHLDTLRATAQEAQSLGGRCVPVVCDSSQESEVKSLFEQVdREQQGRLD 87
Cdd:pfam00106   1 KVALVTGASSGIGRAIAKRLAKEGAKVVLVDRSEEKLEAVAKELGALGGKALFIQGDVTDRAQVKALVEQA-VERLGRLD 79

                          90
                  ....*....|....*...
gi 1958679612  88 VLVNNayAGVQCDKLAAD 105
Cdd:pfam00106  80 ILVNN--AGITGLGPFSE 95

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958679612    9 VCVVTGASRGIGRGIALQLCQAGA-TVYITGRH---LDTLRATAQEAQSLGGRCVPVVCDSSQESEVKSLFEQVdREQQG 84
Cdd:smart00822   2 TYLITGGLGGLGRALARWLAERGArRLVLLSRSgpdAPGAAALLAELEAAGARVTVVACDVADRDALAAVLAAI-PAVEG 80

                           90       100
                   ....*....|....*....|.
gi 1958679612   85 RLDVLVNNayAGVQCDKLAAD 105
Cdd:smart00822  81 PLTGVIHA--AGVLDDGVLAS 99

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 1958679612   5 MKGQVCVVTGASRGIGRGIALQLCQAGATVYITGRHL--------DTLRAT----AQEAQSLGGRCVPVVCDSSQESEVK 72
Cdd:cd05338     1 LSGKVAFVTGASRGIGRAIALRLAKAGATVVVAAKTAsegdngsaKSLPGTieetAEEIEAAGGQALPIVVDVRDEDQVR 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958679612  73 SLFEQVDrEQQGRLDVLVNNAYAGVQ------------------------------------------------------ 98
Cdd:cd05338    81 ALVEATV-DQFGRLDILVNNAGAIWLslvedtpakrfdlmqrvnlrgtyllsqaalphmvkagqghilnispplslrpar 159

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958679612  99 -----------CDKLAADCAHELRRHGVSYVSLWPGLVQTemvkeyvakeeqpedplfkkmksvlsSAETTEMSGKCVVA 167
Cdd:cd05338   160 gdvayaagkagMSRLTLGLAAELRRHGIAVNSLWPSTAIE--------------------------TPAATELSGGSDPA 213

                         250       260       270
                  ....*....|....*....|....*....|...
gi 1958679612 168 LATDPNILSLSGKVLPSCDLARRYGLKDVDGRP 200
Cdd:cd05338   214 RARSPEILSDAVLAILSRPAAERTGLVVIDEEL 246

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 1958679612   3 MT-MKGQVCVVTGASRGIGRGIALQLCQAGATVYITGRHLDTLRATAQEAQSLGGRCVPVVCDSSQESEVKSLFEQVdRE 81
Cdd:COG1028     1 MTrLKGKVALVTGGSSGIGRAIARALAAEGARVVITDRDAEALEAAAAELRAAGGRALAVAADVTDEAAVEALVAAA-VA 79

                          90       100
                  ....*....|....*....|....
gi 1958679612  82 QQGRLDVLVNNayAGVQCDKLAAD 105
Cdd:COG1028    80 AFGRLDILVNN--AGITPPGPLEE 101

Short-chain dehydrogenase [General function prediction only];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958679612   3 MTMKGQVCVVTGASRGIGRGIALQLCQAGATVYITGRHLDTLRATAQEAQSLGGRCVPVVCDSSQESEVKSLFEQVdREQ 82
Cdd:COG0300     1 MSLTGKTVLITGASSGIGRALARALAARGARVVLVARDAERLEALAAELRAAGARVEVVALDVTDPDAVAALAEAV-LAR 79

                          90
                  ....*....|.
gi 1958679612  83 QGRLDVLVNNA 93
Cdd:COG0300    80 FGPIDVLVNNA 90

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 1958679612  10 CVVTGASRGIGRGIALQLCQAGATVYITGRHLDTLRATAqEAQSLGGRCVPVVCDSSQESEVKSLFEQVdREQQGRLDVL 89
Cdd:cd05233     1 ALVTGASSGIGRAIARRLAREGAKVVLADRNEEALAELA-AIEALGGNAVAVQADVSDEEDVEALVEEA-LEEFGRLDIL 78

                  ....
gi 1958679612  90 VNNA 93
Cdd:cd05233    79 VNNA 82

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958679612   8 QVCVVTGASRGIGRGIALQLCQAGATVYITGRHLDTLRATAQEAQSLGGRCVPVVCDSSQESEVKSLFEQVdREQQGRLD 87
Cdd:pfam00106   1 KVALVTGASSGIGRAIAKRLAKEGAKVVLVDRSEEKLEAVAKELGALGGKALFIQGDVTDRAQVKALVEQA-VERLGRLD 79

                          90
                  ....*....|....*...
gi 1958679612  88 VLVNNayAGVQCDKLAAD 105
Cdd:pfam00106  80 ILVNN--AGITGLGPFSE 95

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 1958679612   8 QVCVVTGASRGIGRGIALQLCQAGATVYITGRHLDTLRATAQEAQSLGGRCVPVVCDSSQESEVKSLFEQVDREqQGRLD 87
Cdd:cd05333     1 KVALVTGASRGIGRAIALRLAAEGAKVAVTDRSEEAAAETVEEIKALGGNAAALEADVSDREAVEALVEKVEAE-FGPVD 79

                          90
                  ....*....|....*
gi 1958679612  88 VLVNNayAGVQCDKL 102
Cdd:cd05333    80 ILVNN--AGITRDNL 92

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 1958679612   5 MKGQVCVVTGASRGIGRGIALQLCQAGATVYITGRHLDTLRATAQEAQSL-GGRCVPVVCDSSQESEVKSLFEQVDREqQ 83
Cdd:cd05369     1 LKGKVAFITGGGTGIGKAIAKAFAELGASVAIAGRKPEVLEAAAEEISSAtGGRAHPIQCDVRDPEAVEAAVDETLKE-F 79

                          90
                  ....*....|...
gi 1958679612  84 GRLDVLVNNAyAG 96
Cdd:cd05369    80 GKIDILINNA-AG 91

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958679612   5 MKGQVCVVTGASRGIGRGIALQLCQAGATVYIT-GRHLDTLRATAQEAQSLGGRCVPVVCDSSQESEVKSLFEQVDrEQQ 83
Cdd:PRK08063    2 FSGKVALVTGSSRGIGKAIALRLAEEGYDIAVNyARSRKAAEETAEEIEALGRKALAVKANVGDVEKIKEMFAQID-EEF 80

                          90
                  ....*....|....
gi 1958679612  84 GRLDVLVNNAYAGV 97
Cdd:PRK08063   81 GRLDVFVNNAASGV 94

SDR family oxidoreductase;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958679612   3 MTMKGQVCVVTGASRGIGRGIALQLCQAGATVYITGRHLDTLRATAQEAQSlGGRCVPVVCDSSQESEVKSLFEQVdREQ 82
Cdd:PRK07231    1 MRLEGKVAIVTGASSGIGEGIARRFAAEGARVVVTDRNEEAAERVAAEILA-GGRAIAVAADVSDEADVEAAVAAA-LER 78

                          90
                  ....*....|.
gi 1958679612  83 QGRLDVLVNNA 93
Cdd:PRK07231   79 FGSVDILVNNA 89

RhlG and related beta-ketoacyl reductases, classical (c) SDRs; Pseudomonas aeruginosa RhlG is an SDR-family beta-ketoacyl reductase involved in Rhamnolipid biosynthesis. RhlG is similar to but distinct from the FabG family of beta-ketoacyl-acyl carrier protein (ACP) of type II fatty acid synthesis. RhlG and related proteins are classical SDRs, with a canonical active site tetrad and glycine-rich NAD(P)-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 1958679612   4 TMKGQVCVVTGASRGIGRGIALQLCQAGATVYITGRHLDTLRATAQEAQSLgGRCVPVVCDSSQESEVKSLFEQVdREQQ 83
Cdd:cd08942     3 SVAGKIVLVTGGSRGIGRMIAQGFLEAGARVIISARKAEACADAAEELSAY-GECIAIPADLSSEEGIEALVARV-AERS 80

                          90
                  ....*....|...
gi 1958679612  84 GRLDVLVNNAYAG 96
Cdd:cd08942    81 DRLDVLVNNAGAT 93

SDR family oxidoreductase;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958679612   3 MTMKGQVCVVTGASRGIGRGIALQLCQAGATVYITGRHLDTLRATAQEAQSlGGRCVPVVCDSSQESEVKSLFEQVDREq 82
Cdd:PRK07326    2 MSLKGKVALITGGSKGIGFAIAEALLAEGYKVAITARDQKELEEAAAELNN-KGNVLGLAADVRDEADVQRAVDAIVAA- 79

                          90
                  ....*....|....*
gi 1958679612  83 QGRLDVLVNNAYAGV 97
Cdd:PRK07326   80 FGGLDVLIANAGVGH 94

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 1958679612   7 GQVCVVTGASRGIGRGIALQLCQAGATVYITGRHLDTLRATAQEAQSLGGRCVPVVCDSSQESEVKSLFEQVdREQQGRL 86
Cdd:cd05344     1 GKVALVTAASSGIGLAIARALAREGARVAICARNRENLERAASELRAGGAGVLAVVADLTDPEDIDRLVEKA-GDAFGRV 79

                  ....*..
gi 1958679612  87 DVLVNNA 93
Cdd:cd05344    80 DILVNNA 86

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 1958679612  12 VTGASRGIGRGIALQLCQAGATVYITGRH-LDTLRATAQEAQSLGGRCVPVVCDSSQESEVKSLFEQVdREQQGRLDVLV 90
Cdd:cd05359     3 VTGGSRGIGKAIALRLAERGADVVINYRKsKDAAAEVAAEIEELGGKAVVVRADVSQPQDVEEMFAAV-KERFGRLDVLV 81

                  ....*..
gi 1958679612  91 NNAYAGV 97
Cdd:cd05359    82 SNAAAGA 88

clavulanic acid dehydrogenase (CAD), classical (c) SDR; CAD catalyzes the NADP-dependent reduction of clavulanate-9-aldehyde to clavulanic acid, a beta-lactamase inhibitor. SDRs are a functionally diverse family of oxidoreductases that have a single domain with a structurally conserved Rossmann fold (alpha/beta folding pattern with a central beta-sheet), an NAD(P)(H)-binding region, and a structurally diverse C-terminal region. Classical SDRs are typically about 250 residues long, while extended SDRs are approximately 350 residues. Sequence identity between different SDR enzymes are typically in the 15-30% range, but the enzymes share the Rossmann fold NAD-binding motif and characteristic NAD-binding and catalytic sequence patterns. These enzymes catalyze a wide range of activities including the metabolism of steroids, cofactors, carbohydrates, lipids, aromatic compounds, and amino acids, and act in redox sensing. Classical SDRs have an TGXXX[AG]XG cofactor binding motif and a YXXXK active site motif, with the Tyr residue of the active site motif serving as a critical catalytic residue (Tyr-151, human 15-hydroxyprostaglandin dehydrogenase (15-PGDH) numbering). In addition to the Tyr and Lys, there is often an upstream Ser (Ser-138, 15-PGDH numbering) and/or an Asn (Asn-107, 15-PGDH numbering) contributing to the active site; while substrate binding is in the C-terminal region, which determines specificity. The standard reaction mechanism is a 4-pro-S hydride transfer and proton relay involving the conserved Tyr and Lys, a water molecule stabilized by Asn, and nicotinamide. Extended SDRs have additional elements in the C-terminal region, and typically have a TGXXGXXG cofactor binding motif. Complex (multidomain) SDRs such as ketoreductase domains of fatty acid synthase have a GGXGXXG NAD(P)-binding motif and an altered active site motif (YXXXN). Fungal type ketoacyl reductases have a TGXXXGX(1-2)G NAD(P)-binding motif. Some atypical SDRs have lost catalytic activity and/or have an unusual NAD(P)-binding motif and missing or unusual active site residues. Reactions catalyzed within the SDR family include isomerization, decarboxylation, epimerization, C=N bond reduction, dehydratase activity, dehalogenation, Enoyl-CoA reduction, and carbonyl-alcohol oxidoreduction.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958679612   5 MKGQVCVVTGASRGIGRGIALQLCQAGATVYITGRHLDTLRATAQEAQSLGGRCVPVVCDSSQESEVKSLFEQVdREQQG 84
Cdd:cd08934     1 LQGKVALVTGASSGIGEATARALAAEGAAVAIAARRVDRLEALADELEAEGGKALVLELDVTDEQQVDAAVERT-VEALG 79

                  ....*....
gi 1958679612  85 RLDVLVNNA 93
Cdd:cd08934    80 RLDILVNNA 88

SDR family oxidoreductase;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958679612   1 MIMTMKGQVCVVTGASRGIGRGIALQLCQAGATVYITGRHLDTLRATAQEAQSLGGRCVPVVCDSSQESEVKSLFEQVdR 80
Cdd:PRK06172    1 MSMTFSGKVALVTGGAAGIGRATALAFAREGAKVVVADRDAAGGEETVALIREAGGEALFVACDVTRDAEVKALVEQT-I 79

                          90       100
                  ....*....|....*....|...
gi 1958679612  81 EQQGRLDVLVNNAYAGVQCDKLA 103
Cdd:PRK06172   80 AAYGRLDYAFNNAGIEIEQGRLA 102

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        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958679612   5 MKGQVCVVTGASRGIGRGIALQLCQAGATVYITGRHLDTLRATAQEAQSLGGRCVP---VVCDSSQESEVKSLFEQVdRE 81
Cdd:cd05364     1 LSGKVAIITGSSSGIGAGTAILFARLGARLALTGRDAERLEETRQSCLQAGVSEKKillVVADLTEEEGQDRIISTT-LA 79

                          90
                  ....*....|..
gi 1958679612  82 QQGRLDVLVNNA 93
Cdd:cd05364    80 KFGRLDILVNNA 91

short chain dehydrogenase; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958679612   5 MKGQVCVVTGASRGIGRGIALQLCQAGATVYITGRHLDTLRATAQEAQSLGGRCVPVVCDSSQESEVKSLFEQVdREQQG 84
Cdd:PRK12939    5 LAGKRALVTGAARGLGAAFAEALAEAGATVAFNDGLAAEARELAAALEAAGGRAHAIAADLADPASVQRFFDAA-AAALG 83

                          90       100
                  ....*....|....*....|..
gi 1958679612  85 RLDVLVNNayAGVQCDKLAADC 106
Cdd:PRK12939   84 GLDGLVNN--AGITNSKSATEL 103

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958679612   3 MTMKGQVCVVTGASRGIGRGIALQLCQAGATVYITGRHLDTLRATAQEAQSLGGRCVPVVCDSSQESEVKSLFEQVdREQ 82
Cdd:PRK08217    1 MDLKDKVIVITGGAQGLGRAMAEYLAQKGAKLALIDLNQEKLEEAVAECGALGTEVRGYAANVTDEEDVEATFAQI-AED 79

                          90
                  ....*....|.
gi 1958679612  83 QGRLDVLVNNA 93
Cdd:PRK08217   80 FGQLNGLINNA 90

3-hydroxybutyrate dehydrogenase; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958679612   1 MIMTMKGQVCVVTGASRGIGRGIALQLCQAGATVYITGRHLDTLRATAQEAQSLGGRCVPVVCDSSQESEVKSLFEQVdR 80
Cdd:PRK13394    1 MMSNLNGKTAVVTGAASGIGKEIALELARAGAAVAIADLNQDGANAVADEINKAGGKAIGVAMDVTNEDAVNAGIDKV-A 79

                          90
                  ....*....|....*...
gi 1958679612  81 EQQGRLDVLVNNayAGVQ 98
Cdd:PRK13394   80 ERFGSVDILVSN--AGIQ 95

SDR family oxidoreductase;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958679612   5 MKGQVCVVTGASRGIGRGIALQLCQAGATVYITGRHLDTLRATAQE--AQSLGGRCVPVVCDSSQESEVKSLFEQVDREq 82
Cdd:PRK07063    5 LAGKVALVTGAAQGIGAAIARAFAREGAAVALADLDAALAERAAAAiaRDVAGARVLAVPADVTDAASVAAAVAAAEEA- 83

                          90       100
                  ....*....|....*....|.
gi 1958679612  83 QGRLDVLVNNAYAGVQCDKLA 103
Cdd:PRK07063   84 FGPLDVLVNNAGINVFADPLA 104

short chain dehydrogenase; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958679612   1 MIMTMKGQVCVVTGASRGIGRGIALQLCQAGATVYITGRHLDTLRATAQEAQSLGGRCVPVVCDSSQESEVKSLFEQVDR 80
Cdd:PRK07109    2 MLKPIGRQVVVITGASAGVGRATARAFARRGAKVVLLARGEEGLEALAAEIRAAGGEALAVVADVADAEAVQAAADRAEE 81

                          90
                  ....*....|....*..
gi 1958679612  81 EqQGRLDVLVNNAYAGV 97
Cdd:PRK07109   82 E-LGPIDTWVNNAMVTV 97

SDR family oxidoreductase;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958679612   3 MTMKGQVCVVTGASRGIGRGIALQLCQAGATVYITGRHLDTLRATAQEaQSLGGRCVPVVCDSSQESEVKSLFEQVdrEQ 82
Cdd:PRK09072    1 MDLKDKRVLLTGASGGIGQALAEALAAAGARLLLVGRNAEKLEALAAR-LPYPGRHRWVVADLTSEAGREAVLARA--RE 77

                          90
                  ....*....|.
gi 1958679612  83 QGRLDVLVNNA 93
Cdd:PRK09072   78 MGGINVLINNA 88

7-alpha-hydroxysteroid dehydrogenase; Validated

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958679612   5 MKGQVCVVTGASRGIGRGIALQLCQAGATVYITGRHLDTLRATAQEAQSLGGRCVPVVCDSSQESEVKSLFeQVDREQQG 84
Cdd:PRK06113    9 LDGKCAIITGAGAGIGKEIAITFATAGASVVVSDINADAANHVVDEIQQLGGQAFACRCDITSEQELSALA-DFALSKLG 87

                          90
                  ....*....|..
gi 1958679612  85 RLDVLVNNAYAG 96
Cdd:PRK06113   88 KVDILVNNAGGG 99