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 2427301610   1 TFFITQDVVKNMLADGReGAIVNVGSIGAQAALGDSpaSAYSMAKAGLHALTRNLAIELASAGIRVNAVSPGIVHTPIYE 80
Cdd:cd05233   109 VFLLTRAALPHMKKQGG-GRIVNISSVAGLRPLPGQ--AAYAASKAALEGLTRSLALELAPYGIRVNAVAPGLVDTPMLA 185

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|
gi 2427301610  81 GFMAKEDiAGAMQSLNAFHPLG---DVANTIFFLLSDKASWVTGAIWDVD 127
Cdd:cd05233   186 KLGPEEA-EKELAAAIPLGRLGtpeEVAEAVVFLASDEASYITGQVIPVD 234

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2427301610   2 FFITQDVVKNMLADGReGAIVNVGSIGAQaaLGDSPASAYSMAKAGLHALTRNLAIELASAGIRVNAVSPGIVHTPIYEG 81
Cdd:PRK05565  119 MLLTRYALPYMIKRKS-GVIVNISSIWGL--IGASCEVLYSASKGAVNAFTKALAKELAPSGIRVNAVAPGAIDTEMWSS 195

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....
gi 2427301610  82 FMAKEdiagaMQSLNAFHPLG------DVANTIFFLLSDKASWVTGAIWDVDAG 129
Cdd:PRK05565  196 FSEED-----KEGLAEEIPLGrlgkpeEIAKVVLFLASDDASYITGQIITVDGG 244

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 2427301610   1 TFFITQDVVKNMLADGReGAIVNVGSIGAQAALGDSpaSAYSMAKAGLHALTRNLAIELASAGIRVNAVSPGIVHTPIYE 80
Cdd:cd05233   109 VFLLTRAALPHMKKQGG-GRIVNISSVAGLRPLPGQ--AAYAASKAALEGLTRSLALELAPYGIRVNAVAPGLVDTPMLA 185

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|
gi 2427301610  81 GFMAKEDiAGAMQSLNAFHPLG---DVANTIFFLLSDKASWVTGAIWDVD 127
Cdd:cd05233   186 KLGPEEA-EKELAAAIPLGRLGtpeEVAEAVVFLASDEASYITGQVIPVD 234

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2427301610   2 FFITQDVVKNMLADGReGAIVNVGSIGAQaaLGDSPASAYSMAKAGLHALTRNLAIELASAGIRVNAVSPGIVHTPIYEG 81
Cdd:PRK05565  119 MLLTRYALPYMIKRKS-GVIVNISSIWGL--IGASCEVLYSASKGAVNAFTKALAKELAPSGIRVNAVAPGAIDTEMWSS 195

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....
gi 2427301610  82 FMAKEdiagaMQSLNAFHPLG------DVANTIFFLLSDKASWVTGAIWDVDAG 129
Cdd:PRK05565  196 FSEED-----KEGLAEEIPLGrlgkpeEIAKVVLFLASDDASYITGQIITVDGG 244

3-oxoacyl-ACP reductase FabG;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2427301610   1 TFFITQDVVKNMLADGReGAIVNVGSIGAQAalGDSPASAYSMAKAGLHALTRNLAIELASAGIRVNAVSPGIVHTPIYE 80
Cdd:PRK05653  117 TFNVVRAALPPMIKARY-GRIVNISSVSGVT--GNPGQTNYSAAKAGVIGFTKALALELASRGITVNAVAPGFIDTDMTE 193

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 2427301610  81 GfMAKEDIAGAMQSLnafhPLG------DVANTIFFLLSDKASWVTGAIWDVDAG 129
Cdd:PRK05653  194 G-LPEEVKAEILKEI----PLGrlgqpeEVANAVAFLASDAASYITGQVIPVNGG 243

xylulose reductase-like, classical (c) SDRs; Members of this subgroup include proteins identified as L-xylulose reductase (XR) and carbonyl reductase; they are members of the SDR family. XR, catalyzes the NADP-dependent reduction of L-xyulose and other sugars. Tetrameric mouse carbonyl reductase is involved in the metabolism of biogenic and xenobiotic carbonyl compounds. This subgroup also includes tetrameric chicken liver D-erythrulose reductase, which catalyzes the reduction of D-erythrulose to D-threitol. SDRs are a functionally diverse family of oxidoreductases that have a single domain with a structurally conserved Rossmann fold (alpha/beta folding pattern with a central beta-sheet), an NAD(P)(H)-binding region, and a structurally diverse C-terminal region. Classical SDRs are typically about 250 residues long, while extended SDRS are approximately 350 residues. Sequence identity between different SDR enzymes are typically in the 15-30% range, but the enzymes share the Rossmann fold NAD-binding motif and characteristic NAD-binding and catalytic sequence patterns. These enzymes have a 3-glycine N-terminal NAD(P)(H)-binding pattern (typically, TGxxxGxG in classical SDRs and TGxxGxxG in extended SDRs), while substrate binding is in the C-terminal region. A critical catalytic Tyr residue (Tyr-151, human 15-hydroxyprostaglandin dehydrogenase (15-PGDH) numbering), is often found in a conserved YXXXK pattern. In addition to the Tyr and Lys, there is often an upstream Ser (Ser-138, 15-PGDH numbering) and/or an Asn (Asn-107, 15-PGDH numbering) or additional Ser, contributing to the active site. Substrates for these enzymes include sugars, steroids, alcohols, and aromatic compounds. The standard reaction mechanism is a proton relay involving the conserved Tyr and Lys, as well as Asn (or Ser).

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2427301610   2 FFITQDVVKNMLADGREGAIVNVGSIGAQAALGDSpaSAYSMAKAGLHALTRNLAIELASAGIRVNAVSPGIVHTPIYEG 81
Cdd:cd05351   112 IHVSQIVARGMIARGVPGSIVNVSSQASQRALTNH--TVYCSTKAALDMLTKVMALELGPHKIRVNSVNPTVVMTDMGRD 189

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....
gi 2427301610  82 FMAKEDIAGAMQS---LNAFHPLGDVANTIFFLLSDKASWVTGAIWDVDAGIMA 132
Cdd:cd05351   190 NWSDPEKAKKMLNripLGKFAEVEDVVNAILFLLSDKSSMTTGSTLPVDGGFLA 243

short chain dehydrogenase; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2427301610   2 FFITQDVVKNMLADGREGAIVNVGSIGAQAALGDSpaSAYSMAKAGLHALTRNLAIELASAGIRVNAVSPGIVHTPIYEG 81
Cdd:PRK07060  113 ALVARHVARAMIAAGRGGSIVNVSSQAALVGLPDH--LAYCASKAALDAITRVLCVELGPHGIRVNSVNPTVTLTPMAAE 190

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 2427301610  82 FMAKEDIAGAMQslnAFHPLG------DVANTIFFLLSDKASWVTGAIWDVDAGIMAV 133
Cdd:PRK07060  191 AWSDPQKSGPML---AAIPLGrfaevdDVAAPILFLLSDAASMVSGVSLPVDGGYTAR 245

short chain dehydrogenase; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2427301610   5 TQDVVKNMLADGreGAIVNVGSIGAQAAlgDSPASAYSMAKAGLHALTRNLAIELASAGIRVNAVSPGIVHTPIYEGfMA 84
Cdd:PRK08265  118 AQAAHPHLARGG--GAIVNFTSISAKFA--QTGRWLYPASKAAIRQLTRSMAMDLAPDGIRVNSVSPGWTWSRVMDE-LS 192

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|.
gi 2427301610  85 KEDIAGAMQSLNAFHPLG------DVANTIFFLLSDKASWVTGAIWDVDAG 129
Cdd:PRK08265  193 GGDRAKADRVAAPFHLLGrvgdpeEVAQVVAFLCSDAASFVTGADYAVDGG 243

tropinone reductase-I and II (TR-1, and TR-II)-like, classical (c) SDRs; This subgroup includes TR-I and TR-II; these proteins are members of the SDR family. TRs catalyze the NADPH-dependent reductions of the 3-carbonyl group of tropinone, to a beta-hydroxyl group. TR-I and TR-II produce different stereoisomers from tropinone, TR-I produces tropine (3alpha-hydroxytropane), and TR-II, produces pseudotropine (sigma-tropine, 3beta-hydroxytropane). 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 2427301610  19 GAIVNVGSI-GAQAALGDSPasaYSMAKAGLHALTRNLAIELASAGIRVNAVSPGIVHTPIYEGFMAKEDIAGAMQSLNA 97
Cdd:cd05329   136 GNIVFISSVaGVIAVPSGAP---YGATKGALNQLTRSLACEWAKDNIRVNAVAPWVIATPLVEPVIQQKENLDKVIERTP 212

                          90       100       110
                  ....*....|....*....|....*....|....*...
gi 2427301610  98 FHPLG---DVANTIFFLLSDKASWVTGAIWDVDAGIMA 132
Cdd:cd05329   213 LKRFGepeEVAALVAFLCMPAASYITGQIIAVDGGLTA 250

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 2427301610   2 FFITQDVVKNMLADGrEGAIVNVGSIGAQAALgdSPASAYSMAKAGLHALTRNLAIELASAGIRVNAVSPGIVHTPIYEG 81
Cdd:cd05359   112 VHCAQQAAKLMRERG-GGRIVAISSLGSIRAL--PNYLAVGTAKAALEALVRYLAVELGPRGIRVNAVSPGVIDTDALAH 188

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....
gi 2427301610  82 FMAKEDiagAMQSLNAFHPLG------DVANTIFFLLSDKASWVTGAIWDVDAG 129
Cdd:cd05359   189 FPNRED---LLEAAAANTPAGrvgtpqDVADAVGFLCSDAARMITGQTLVVDGG 239

SDR family oxidoreductase;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2427301610   2 FFITQDVVKNMLADGREGAIVNVGSIGAQAALGDspASAYSMAKAGLHALTRNLAIELASAGIRVNAVSPGIVHTPiyeg 81
Cdd:PRK12743  116 FLCSQIAARHMVKQGQGGRIINITSVHEHTPLPG--ASAYTAAKHALGGLTKAMALELVEHGILVNAVAPGAIATP---- 189

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 2427301610  82 fMAKEDIAGAMQSLNAFHPLG------DVANTIFFLLSDKASWVTGAIWDVDAGIMA 132
Cdd:PRK12743  190 -MNGMDDSDVKPDSRPGIPLGrpgdthEIASLVAWLCSEGASYTTGQSLIVDGGFML 245

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2427301610   1 TFFITQDVVKNMLADGRegaIVNVGSIGAQAALGDspASAYSMAKAGLHALTRNLAIELASAGIRVNAVSPGIVHTPIYE 80
Cdd:cd05362   116 AFFVLQEAAKRLRDGGR---IINISSSLTAAYTPN--YGAYAGSKAAVEAFTRVLAKELGGRGITVNAVAPGPVDTDMFY 190

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|...
gi 2427301610  81 GFMAKEDIAGAMQSlNAFHPLG---DVANTIFFLLSDKASWVTGAIWDVDAGI 130
Cdd:cd05362   191 AGKTEEAVEGYAKM-SPLGRLGepeDIAPVVAFLASPDGRWVNGQVIRANGGY 242

short chain dehydrogenase; Validated

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2427301610  19 GAIVNVGSIGAQAALgdSPASAYSMAKAGLHALTRNLAIELASAGIRVNAVSPGIVHTPiyeGFMAKEDIAGA-MQSLNA 97
Cdd:PRK06484  394 GVIVNLGSIASLLAL--PPRNAYCASKAAVTMLSRSLACEWAPAGIRVNTVAPGYIETP---AVLALKASGRAdFDSIRR 468

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|...
gi 2427301610  98 FHPLG------DVANTIFFLLSDKASWVTGAIWDVDAGIMAVR 134
Cdd:PRK06484  469 RIPLGrlgdpeEVAEAIAFLASPAASYVNGATLTVDGGWTAFG 511

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 2427301610   1 TFFITQDVVKNMLADGREGAIVNvgsIGAQAALGDSPASAYS-MAKAGLHALTRNLAIELASAGIRVNAVSPG-IVHTPI 78
Cdd:cd05369   116 TFNTTKAVGKRLIEAKHGGSILN---ISATYAYTGSPFQVHSaAAKAGVDALTRSLAVEWGPYGIRVNAIAPGpIPTTEG 192

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 2427301610  79 YEGFMAKEDIAGAMQSLNafhPLG------DVANTIFFLLSDKASWVTGAIWDVDAG 129
Cdd:cd05369   193 MERLAPSGKSEKKMIERV---PLGrlgtpeEIANLALFLLSDAASYINGTTLVVDGG 246

SDR family oxidoreductase;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2427301610   5 TQDVVKNMLADGrEGAIVNVGSIGAQAALGdspasAYSMAKAGLHALTRNLAIELASAGIRVNAVSPGIVHTPIYEGFMA 84
Cdd:PRK07774  125 TRAVYKHMAKRG-GGAIVNQSSTAAWLYSN-----FYGLAKVGLNGLTQQLARELGGMNIRVNAIAPGPIDTEATRTVTP 198

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*..
gi 2427301610  85 KEDIAGAMQS--LNAFHPLGDVANTIFFLLSDKASWVTGAIWDVDAG 129
Cdd:PRK07774  199 KEFVADMVKGipLSRMGTPEDLVGMCLFLLSDEASWITGQIFNVDGG 245

SDR family oxidoreductase;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2427301610  19 GAIVNVGSIGAQAALGDSpaSAYSMAKAGLHALTRNLAIELASAGIRVNAVSPGIVHTPIY-EGFMAKEDIAGAMQSLNA 97
Cdd:PRK06138  133 GSIVNTASQLALAGGRGR--AAYVASKGAIASLTRAMALDHATDGIRVNAVAPGTIDTPYFrRIFARHADPEALREALRA 210

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|.
gi 2427301610  98 FHPLG------DVANTIFFLLSDKASWVTGAIWDVDAGIMA 132
Cdd:PRK06138  211 RHPMNrfgtaeEVAQAALFLASDESSFATGTTLVVDGGWLA 251

short chain dehydrogenase; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2427301610   2 FFITQDVVKNMLADGREGAIVNVGSIGAQAalGDSPASAYSMAKAGLHALTRNLAIELASAGIRVNAVSPGIVHTP---- 77
Cdd:PRK06198  120 FFLMQEAIKLMRRRKAEGTIVNIGSMSAHG--GQPFLAAYCASKGALATLTRNAAYALLRNRIRVNGLNIGWMATEgedr 197

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 2427301610  78 IYEGFMAKED--IAGAMQSLnafhPLG------DVANTIFFLLSDKASWVTGAIWDVDAGIM 131
Cdd:PRK06198  198 IQREFHGAPDdwLEKAAATQ----PFGrlldpdEVARAVAFLLSDESGLMTGSVIDFDQSVW 255

short chain dehydrogenase; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2427301610   1 TFFITQDVVKNMLADGREGAIVNVGSI---GAQAALGdspasAYSMAKAGLHALTRNLAIELASAGIRVNAVSPGIVHTP 77
Cdd:PRK12827  122 FFNVTQAALPPMIRARRGGRIVNIASVagvRGNRGQV-----NYAASKAGLIGLTKTLANELAPRGITVNAVAPGAINTP 196

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|..
gi 2427301610  78 IYEGFMAKEDIAGAMqSLNAFHPLGDVANTIFFLLSDKASWVTGAIWDVDAG 129
Cdd:PRK12827  197 MADNAAPTEHLLNPV-PVQRLGEPDEVAALVAFLVSDAASYVTGQVIPVDGG 247

classical (c) SDR, subgroup 12; These are classical SDRs, with the canonical active site tetrad and glycine-rich NAD-binding motif. SDRs are a functionally diverse family of oxidoreductases that have a single domain with a structurally conserved Rossmann fold (alpha/beta folding pattern with a central beta-sheet), an NAD(P)(H)-binding region, and a structurally diverse C-terminal region. Classical SDRs are typically about 250 residues long, while extended SDRs are approximately 350 residues. Sequence identity between different SDR enzymes are typically in the 15-30% range, but the enzymes share the Rossmann fold NAD-binding motif and characteristic NAD-binding and catalytic sequence patterns. These enzymes catalyze a wide range of activities including the metabolism of steroids, cofactors, carbohydrates, lipids, aromatic compounds, and amino acids, and act in redox sensing. Classical SDRs have an TGXXX[AG]XG cofactor binding motif and a YXXXK active site motif, with the Tyr residue of the active site motif serving as a critical catalytic residue (Tyr-151, human 15-hydroxyprostaglandin dehydrogenase (15-PGDH) numbering). In addition to the Tyr and Lys, there is often an upstream Ser (Ser-138, 15-PGDH numbering) and/or an Asn (Asn-107, 15-PGDH numbering) contributing to the active site; while substrate binding is in the C-terminal region, which determines specificity. The standard reaction mechanism is a 4-pro-S hydride transfer and proton relay involving the conserved Tyr and Lys, a water molecule stabilized by Asn, and nicotinamide. Extended SDRs have additional elements in the C-terminal region, and typically have a TGXXGXXG cofactor binding motif. Complex (multidomain) SDRs such as ketoreductase domains of fatty acid synthase have a GGXGXXG NAD(P)-binding motif and an altered active site motif (YXXXN). Fungal type ketoacyl reductases have a TGXXXGX(1-2)G NAD(P)-binding motif. Some atypical SDRs have lost catalytic activity and/or have an unusual NAD(P)-binding motif and missing or unusual active site residues. Reactions catalyzed within the SDR family include isomerization, decarboxylation, epimerization, C=N bond reduction, dehydratase activity, dehalogenation, Enoyl-CoA reduction, and carbonyl-alcohol oxidoreduction.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2427301610  19 GAIVNVGSIGAQAalGDSPASAYSMAKAGLHALTRNLAIELASAGIRVNAVSPGIVHTPI----YEGFMAKEDIAGAMQS 94
Cdd:cd08944   130 GSIVNLSSIAGQS--GDPGYGAYGASKAAIRNLTRTLAAELRHAGIRCNALAPGLIDTPLllakLAGFEGALGPGGFHLL 207

                          90       100       110
                  ....*....|....*....|....*....|....*....
gi 2427301610  95 LNAFHP-LG---DVANTIFFLLSDKASWVTGAIWDVDAG 129
Cdd:cd08944   208 IHQLQGrLGrpeDVAAAVVFLLSDDASFITGQVLCVDGG 246

SDR family oxidoreductase;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2427301610   4 ITQDVVKNMLaDGREGAIVNVGSigaQAALGDSPASAYSMAKAGLHALTRNLAIELASAGIRVNAVSPGIVHTPIY-EGF 82
Cdd:PRK07577  106 VTQAFLEGMK-LREQGRIVNICS---RAIFGALDRTSYSAAKSALVGCTRTWALELAEYGITVNAVAPGPIETELFrQTR 181

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|
gi 2427301610  83 MAKEDIAGAMQSLNAFHPLG---DVANTIFFLLSDKASWVTGAIWDVDAG 129
Cdd:PRK07577  182 PVGSEEEKRVLASIPMRRLGtpeEVAAAIAFLLSDDAGFITGQVLGVDGG 231

2,3 dihydro-2,3 dihydrozybenzoate dehydrogenases, classical (c) SDRs; 2,3 dihydro-2,3 dihydrozybenzoate dehydrogenase shares the characteristics of the classical SDRs. This subgroup includes Escherichai coli EntA which catalyzes the NAD+-dependent oxidation of 2,3-dihydro-2,3-dihydroxybenzoate to 2,3-dihydroxybenzoate during biosynthesis of the siderophore Enterobactin. 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 2427301610   2 FFITQDVVKNMLaDGREGAIVNVGSIGAQAALGDspASAYSMAKAGLHALTRNLAIELASAGIRVNAVSPGIVHTPIYEG 81
Cdd:cd05331   104 FNLLQAVAPHMK-DRRTGAIVTVASNAAHVPRIS--MAAYGASKAALASLSKCLGLELAPYGVRCNVVSPGSTDTAMQRT 180

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 2427301610  82 FMAKED-----IAGAMQSLNAFHPLG------DVANTIFFLLSDKASWVTGAIWDVDAG 129
Cdd:cd05331   181 LWHDEDgaaqvIAGVPEQFRLGIPLGkiaqpaDIANAVLFLASDQAGHITMHDLVVDGG 239

gluconate 5-dehydrogenase; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2427301610   1 TFFITQDVVKNMLADGREGAIVNVGSIgaqAALGDSP-----ASAYSMAKAGLHALTRNLAIELASAGIRVNAVSPGIVH 75
Cdd:PRK08213  124 LFLLSQAVAKRSMIPRGYGRIINVASV---AGLGGNPpevmdTIAYNTSKGAVINFTRALAAEWGPHGIRVNAIAPGFFP 200

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 2427301610  76 TPiyegfMAKEDIAGAMQSLNAFHPLG------DVANTIFFLLSDKASWVTGAIWDVDAGIMAV 133
Cdd:PRK08213  201 TK-----MTRGTLERLGEDLLAHTPLGrlgddeDLKGAALLLASDASKHITGQILAVDGGVSAV 259