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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005341  27 GIDRKGVLANRVAVVTGSTSGIGFAIARRLARDGAHVVISSRKQQNVDRAMAKLQGEGLSVAGIVCHVGKAEDREQLVAK 106
Cdd:cd08936    1 GVTRRDPLANKVALVTASTDGIGLAIARRLAQDGAHVVVSSRKQQNVDRAVATLQGEGLSVTGTVCHVGKAEDRERLVAT 80

                         90       100       110
                 ....*....|....*....|....*....|....
gi 974005341 107 ALEHCGGVDFLVCSAGVNPLVGSTLGTSEQIWDK 140
Cdd:cd08936   81 AVNLHGGVDILVSNAAVNPFFGNILDSTEEVWDK 114

Porcine peroxisomal carbonyl reductase like, classical (c) SDR; This subgroup contains porcine peroxisomal carbonyl reductase and similar proteins. The porcine enzyme efficiently reduces retinals. This subgroup also includes human dehydrogenase/reductase (SDR family) member 4 (DHRS4), and human DHRS4L1. DHRS4 is a peroxisomal enzyme with 3beta-hydroxysteroid dehydrogenase activity; it catalyzes the reduction of 3-keto-C19/C21-steroids into 3beta-hydroxysteroids more efficiently than it does the retinal reduction. The human DHRS4 gene cluster contains DHRS4, DHRS4L2 and DHRS4L1. DHRS4L2 and DHRS4L1 are paralogs of DHRS4, DHRS4L2 being the most recent member. 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 974005341  27 GIDRKGVLANRVAVVTGSTSGIGFAIARRLARDGAHVVISSRKQQNVDRAMAKLQGEGLSVAGIVCHVGKAEDREQLVAK 106
Cdd:cd08936    1 GVTRRDPLANKVALVTASTDGIGLAIARRLAQDGAHVVVSSRKQQNVDRAVATLQGEGLSVTGTVCHVGKAEDRERLVAT 80

                         90       100       110
                 ....*....|....*....|....*....|....
gi 974005341 107 ALEHCGGVDFLVCSAGVNPLVGSTLGTSEQIWDK 140
Cdd:cd08936   81 AVNLHGGVDILVSNAAVNPFFGNILDSTEEVWDK 114

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 974005341  34 LANRVAVVTGSTSGIGFAIARRLARDGAHVVISSRKQQNVDRAMAKLQGEGLSVAGIVCHVGKAEDREQLVAKALEHCGG 113
Cdd:COG1028    4 LKGKVALVTGGSSGIGRAIARALAAEGARVVITDRDAEALEAAAAELRAAGGRALAVAADVTDEAAVEALVAAAVAAFGR 83

                         90       100
                 ....*....|....*....|....*..
gi 974005341 114 VDFLVCSAGVNPlVGSTLGTSEQIWDK 140
Cdd:COG1028   84 LDILVNNAGITP-PGPLEELTEEDWDR 109

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 974005341    40 VVTGSTSGIGFAIARRLARDGA-HVVISSR---KQQNVDRAMAKLQGEGLSVAGIVCHVGKAEDREQLVAKALEHCGGVD 115
Cdd:smart00822   4 LITGGLGGLGRALARWLAERGArRLVLLSRsgpDAPGAAALLAELEAAGARVTVVACDVADRDALAAVLAAIPAVEGPLT 83

                   ....*...
gi 974005341   116 FLVCSAGV 123
Cdd:smart00822  84 GVIHAAGV 91

Porcine peroxisomal carbonyl reductase like, classical (c) SDR; This subgroup contains porcine peroxisomal carbonyl reductase and similar proteins. The porcine enzyme efficiently reduces retinals. This subgroup also includes human dehydrogenase/reductase (SDR family) member 4 (DHRS4), and human DHRS4L1. DHRS4 is a peroxisomal enzyme with 3beta-hydroxysteroid dehydrogenase activity; it catalyzes the reduction of 3-keto-C19/C21-steroids into 3beta-hydroxysteroids more efficiently than it does the retinal reduction. The human DHRS4 gene cluster contains DHRS4, DHRS4L2 and DHRS4L1. DHRS4L2 and DHRS4L1 are paralogs of DHRS4, DHRS4L2 being the most recent member. 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 974005341  27 GIDRKGVLANRVAVVTGSTSGIGFAIARRLARDGAHVVISSRKQQNVDRAMAKLQGEGLSVAGIVCHVGKAEDREQLVAK 106
Cdd:cd08936    1 GVTRRDPLANKVALVTASTDGIGLAIARRLAQDGAHVVVSSRKQQNVDRAVATLQGEGLSVTGTVCHVGKAEDRERLVAT 80

                         90       100       110
                 ....*....|....*....|....*....|....
gi 974005341 107 ALEHCGGVDFLVCSAGVNPLVGSTLGTSEQIWDK 140
Cdd:cd08936   81 AVNLHGGVDILVSNAAVNPFFGNILDSTEEVWDK 114

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 974005341  34 LANRVAVVTGSTSGIGFAIARRLARDGAHVVISSRKQQNVDRAMAKLQGEGLSVAGIVCHVGKAEDREQLVAKALEHCGG 113
Cdd:COG1028    4 LKGKVALVTGGSSGIGRAIARALAAEGARVVITDRDAEALEAAAAELRAAGGRALAVAADVTDEAAVEALVAAAVAAFGR 83

                         90       100
                 ....*....|....*....|....*..
gi 974005341 114 VDFLVCSAGVNPlVGSTLGTSEQIWDK 140
Cdd:COG1028   84 LDILVNNAGITP-PGPLEELTEEDWDR 109

3-oxoacyl-ACP reductase FabG;

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005341  34 LANRVAVVTGSTSGIGFAIARRLARDGAHVVISSRKQQNVDRAMAKLQGEGLSVAGIVCHVGKAEDREQLVAKALEHCGG 113
Cdd:PRK05653   3 LQGKTALVTGASRGIGRAIALRLAADGAKVVIYDSNEEAAEALAAELRAAGGEARVLVFDVSDEAAVRALIEAAVEAFGA 82

                         90       100
                 ....*....|....*....|....*..
gi 974005341 114 VDFLVCSAGVNPlVGSTLGTSEQIWDK 140
Cdd:PRK05653  83 LDILVNNAGITR-DALLPRMSEEDWDR 108

SDR family oxidoreductase;

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005341  33 VLANRVAVVTGSTSGIGFAIARRLARDGAHVVISSRKQQNVDRAMAKLQGEGlSVAGIVCHVGKAEDREQLVAKALEHCG 112
Cdd:PRK07326   3 SLKGKVALITGGSKGIGFAIAEALLAEGYKVAITARDQKELEEAAAELNNKG-NVLGLAADVRDEADVQRAVDAIVAAFG 81

                         90
                 ....*....|.
gi 974005341 113 GVDFLVCSAGV 123
Cdd:PRK07326  82 GLDVLIANAGV 92

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005341   37 RVAVVTGSTSGIGFAIARRLARDGAHVVISSRKQQNVDRAMAKLQGEGLSVAGIVCHVGKAEDREQLVAKALEHCGGVDF 116
Cdd:pfam00106   1 KVALVTGASSGIGRAIAKRLAKEGAKVVLVDRSEEKLEAVAKELGALGGKALFIQGDVTDRAQVKALVEQAVERLGRLDI 80

                          90       100
                  ....*....|....*....|....
gi 974005341  117 LVCSAGVNPlVGSTLGTSEQIWDK 140
Cdd:pfam00106  81 LVNNAGITG-LGPFSELSDEDWER 103

SDR family oxidoreductase;

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005341  34 LANRVAVVTGSTSGIGFAIARRLARDGAHVVISSRKQQNVDRAMAKLQGEGLSVAGIVCHVGKAEDREQLVAKALEHCGG 113
Cdd:PRK07035   6 LTGKIALVTGASRGIGEAIAKLLAQQGAHVIVSSRKLDGCQAVADAIVAAGGKAEALACHIGEMEQIDALFAHIRERHGR 85

                         90       100
                 ....*....|....*....|....*..
gi 974005341 114 VDFLVCSAGVNPLVGSTLGTSEQIWDK 140
Cdd:PRK07035  86 LDILVNNAAANPYFGHILDTDLGAFQK 112

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005341  35 ANRVAVVTGSTSGIGFAIARRLARDGAHVVISSRKQQNVDRAMAKLQGEglsVAGIVCHVGKAEDREQLVAKALEHCGGV 114
Cdd:COG4221    4 KGKVALITGASSGIGAATARALAAAGARVVLAARRAERLEALAAELGGR---ALAVPLDVTDEAAVEAAVAAAVAEFGRL 80

                         90       100
                 ....*....|....*....|....*.
gi 974005341 115 DFLVCSAGVNPLvGSTLGTSEQIWDK 140
Cdd:COG4221   81 DVLVNNAGVALL-GPLEELDPEDWDR 105

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005341  31 KGVLANRVAVVTGSTSGIGFAIARRLARDGAHVVISSRK-QQNVDRAMAKLQGEGLSVAGIVCHVGKAEDREQLVAKALE 109
Cdd:PRK12825   1 MGSLMGRVALVTGAARGLGRAIALRLARAGADVVVHYRSdEEAAEELVEAVEALGRRAQAVQADVTDKAALEAAVAAAVE 80

                         90
                 ....*....|....*.
gi 974005341 110 HCGGVDFLVCSAGVNP 125
Cdd:PRK12825  81 RFGRIDILVNNAGIFE 96

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 974005341  34 LANRVAVVTGSTSGIGFAIARRLARDGAHVVISSRKQQNVDRAMAKLQGEGL-SVAGIVCHVGKAEDREQLVAKALEHCG 112
Cdd:cd05369    1 LKGKVAFITGGGTGIGKAIAKAFAELGASVAIAGRKPEVLEAAAEEISSATGgRAHPIQCDVRDPEAVEAAVDETLKEFG 80

                         90
                 ....*....|..
gi 974005341 113 GVDFLVCSAGVN 124
Cdd:cd05369   81 KIDILINNAAGN 92

SDR family oxidoreductase;

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005341  36 NRVAVVTGSTSGIGFAIARRLARDGAHVVISSRKQQNVDRAMAKLQGEGLSVAGIVCHVGKAEDREQLVAKALEHCGGVD 115
Cdd:PRK06181   1 GKVVIITGASEGIGRALAVRLARAGAQLVLAARNETRLASLAQELADHGGEALVVPTDVSDAEACERLIEAAVARFGGID 80

                 ....*...
gi 974005341 116 FLVCSAGV 123
Cdd:PRK06181  81 ILVNNAGI 88

gluconate 5-dehydrogenase; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005341  34 LANRVAVVTGSTSGIGFAIARRLARDGAHVVISSRKQQNVDRAMAKLQGEGLSVAGIVCHVGKAEDREQLVAKALEHCGG 113
Cdd:PRK07097   8 LKGKIALITGASYGIGFAIAKAYAKAGATIVFNDINQELVDKGLAAYRELGIEAHGYVCDVTDEDGVQAMVSQIEKEVGV 87

                         90
                 ....*....|
gi 974005341 114 VDFLVCSAGV 123
Cdd:PRK07097  88 IDILVNNAGI 97

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005341  34 LANRVAVVTGSTSGIGFAIARRLARDGAHVVISSRKQQNVDRAMAKLQGE-GLSVAGIVCHVGKAEDREQLVAKALEHCG 112
Cdd:PRK05557   3 LEGKVALVTGASRGIGRAIAERLAAQGANVVINYASSEAGAEALVAEIGAlGGKALAVQGDVSDAESVERAVDEAKAEFG 82

                         90
                 ....*....|.
gi 974005341 113 GVDFLVCSAGV 123
Cdd:PRK05557  83 GVDILVNNAGI 93

short chain dehydrogenase; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005341  34 LANRVAVVTGSTSGIGFAIARRLARDGAHVVISSRKQQNVDRAMAKLQGEGLSVAGIVCHVGKAEDREQLVAKALEHCGG 113
Cdd:PRK12939   5 LAGKRALVTGAARGLGAAFAEALAEAGATVAFNDGLAAEARELAAALEAAGGRAHAIAADLADPASVQRFFDAAAAALGG 84

                         90       100
                 ....*....|....*....|....*..
gi 974005341 114 VDFLVCSAGVNPLVGSTlGTSEQIWDK 140
Cdd:PRK12939  85 LDGLVNNAGITNSKSAT-ELDIDTWDA 110

Porcine testicular carbonyl reductase (PTCR)-like, classical (c) SDRs; PTCR is a classical SDR which catalyzes the NADPH-dependent reduction of ketones on steroids and prostaglandins. Unlike most SDRs, PTCR functions as a monomer. This subgroup also includes human carbonyl reductase 1 (CBR1) and CBR3. CBR1 is an NADPH-dependent SDR with broad substrate specificity and may be responsible for the in vivo reduction of quinones, prostaglandins, and other carbonyl-containing compounds. In addition it includes poppy NADPH-dependent salutaridine reductase which catalyzes the stereospecific reduction of salutaridine to 7(S)-salutaridinol in the biosynthesis of morphine, and Arabidopsis SDR1,a menthone reductase, which catalyzes the reduction of menthone to neomenthol, a compound with antimicrobial activity; SDR1 can also carry out neomenthol oxidation. 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, 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 974005341  37 RVAVVTGSTSGIGFAIARRLARDGA-HVVISSRKQQNVDRAMAKLQGEGLSVAGIVCHVGKAEDREQLVAKALEHCGGVD 115
Cdd:cd05324    1 KVALVTGANRGIGFEIVRQLAKSGPgTVILTARDVERGQAAVEKLRAEGLSVRFHQLDVTDDASIEAAADFVEEKYGGLD 80

                         90       100
                 ....*....|....*....|....*
gi 974005341 116 FLVCSAGVNPLVGSTLGTSEQIWDK 140
Cdd:cd05324   81 ILVNNAGIAFKGFDDSTPTREQARE 105

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 974005341  34 LANRVAVVTGSTSGIGFAIARRLARDGAHVVISSRKQQNVDRAMAKLQGEGLSVAGIVCHVGKAEDREQLVAKALEHCGG 113
Cdd:cd05329    4 LEGKTALVTGGTKGIGYAIVEELAGLGAEVYTCARNQKELDECLTEWREKGFKVEGSVCDVSSRSERQELMDTVASHFGG 83

                         90       100
                 ....*....|....*....|....
gi 974005341 114 -VDFLVCSAGVNPLVGSTLGTSEQ 136
Cdd:cd05329   84 kLNILVNNAGTNIRKEAKDYTEED 107

Short-chain dehydrogenase involved in D-alanine esterification of teichoic acids [Cell wall/membrane/envelope biogenesis, Lipid transport and metabolism];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005341  34 LANRVAVVTGSTSGIGFAIARRLARDGAHVVISSRKQQNVDRAMAKLQGeglsVAGIVCHVGKAEDREQLVAKALEHCGG 113
Cdd:COG3967    3 LTGNTILITGGTSGIGLALAKRLHARGNTVIITGRREEKLEEAAAANPG----LHTIVLDVADPASIAALAEQVTAEFPD 78

                         90
                 ....*....|
gi 974005341 114 VDFLVCSAGV 123
Cdd:COG3967   79 LNVLINNAGI 88

hypothetical protein; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005341  34 LANRVAVVTGSTSGIGFAIARRLARDGAHVVISSRKQQNVDRAMAKLQGEGLSVAGIVCHVGKAEDREQLVAKALEHCGG 113
Cdd:PRK06194   4 FAGKVAVITGAASGFGLAFARIGAALGMKLVLADVQQDALDRAVAELRAQGAEVLGVRTDVSDAAQVEALADAALERFGA 83

                         90
                 ....*....|
gi 974005341 114 VDFLVCSAGV 123
Cdd:PRK06194  84 VHLLFNNAGV 93

short chain dehydrogenase; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005341  31 KGVLANRVAVVTGSTSGIGFAIARRLARDGA-HVVISSRKQQNVDRAMAKLQGEGLSVAGIVCHVGKAEDREQLVAKALE 109
Cdd:PRK06198   1 MGRLDGKVALVTGGTQGLGAAIARAFAERGAaGLVICGRNAEKGEAQAAELEALGAKAVFVQADLSDVEDCRRVVAAADE 80

                         90       100       110
                 ....*....|....*....|....*....|.
gi 974005341 110 HCGGVDFLVCSAGVnPLVGSTLGTSEQIWDK 140
Cdd:PRK06198  81 AFGRLDALVNAAGL-TDRGTILDTSPELFDR 110

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 974005341  34 LANRVAVVTGSTSGIGFAIARRLARDGAHVVISSRKQQNVDRAMAKLQGEGLSVAgivCHVGKAEDREQLVAKALEHCGG 113
Cdd:cd08944    1 LEGKVAIVTGAGAGIGAACAARLAREGARVVVADIDGGAAQAVVAQIAGGALALR---VDVTDEQQVAALFERAVEEFGG 77

                         90       100
                 ....*....|....*....|....*..
gi 974005341 114 VDFLVCSAGVNPLVGSTLGTSEQIWDK 140
Cdd:cd08944   78 LDLLVNNAGAMHLTPAIIDTDLAVWDQ 104

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 974005341  34 LANRVAVVTGSTSGIGFAIARRLARDGAHVVIS-SRKQQNVDRAMAKLQGEGLSVAGIVCHVGKAEDREQLVAKALEHCG 112
Cdd:cd05362    1 LAGKVALVTGASRGIGRAIAKRLARDGASVVVNyASSKAAAEEVVAEIEAAGGKAIAVQADVSDPSQVARLFDAAEKAFG 80

                         90       100
                 ....*....|....*....|....*...
gi 974005341 113 GVDFLVCSAGVNPLvGSTLGTSEQIWDK 140
Cdd:cd05362   81 GVDILVNNAGVMLK-KPIAETSEEEFDR 107

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 974005341  34 LANRVAVVTGSTSGIGFAIARRLARDGAHVVISSRKQQNVD------------RAMAKLQGEGLSVAGIVCHVGKAEDRE 101
Cdd:cd05338    1 LSGKVAFVTGASRGIGRAIALRLAKAGATVVVAAKTASEGDngsakslpgtieETAEEIEAAGGQALPIVVDVRDEDQVR 80

                         90       100       110
                 ....*....|....*....|....*....|....*...
gi 974005341 102 QLVAKALEHCGGVDFLVCSAGVNPLvGSTLGTSEQIWD 139
Cdd:cd05338   81 ALVEATVDQFGRLDILVNNAGAIWL-SLVEDTPAKRFD 117

classical (c) SDR, subgroup 2; Short-chain dehydrogenases/reductases (SDRs, aka Tyrosine-dependent oxidoreductases) 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 974005341  34 LANRVAVVTGSTSGIGFAIARRLARDGAHVVISSRKQQNVDRAmaklQGEGLSVAGIVCHVGKAEDREQLVAKALEHCGG 113
Cdd:cd05370    3 LTGNTVLITGGTSGIGLALARKFLEAGNTVIITGRREERLAEA----KKELPNIHTIVLDVGDAESVEALAEALLSEYPN 78

                         90
                 ....*....|
gi 974005341 114 VDFLVCSAGV 123
Cdd:cd05370   79 LDILINNAGI 88

SDR family oxidoreductase;

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005341  34 LANRVAVVTGSTSGIGFAIARRLARDGAHVVISSRKQQNVDRAMAKL--QGEGLSVAGIVCHVGKAEDREQLVAKALEHC 111
Cdd:PRK09242   7 LDGQTALITGASKGIGLAIAREFLGLGADVLIVARDADALAQARDELaeEFPEREVHGLAADVSDDEDRRAILDWVEDHW 86

                         90
                 ....*....|...
gi 974005341 112 GGVDFLVCSAGVN 124
Cdd:PRK09242  87 DGLHILVNNAGGN 99

SDR family oxidoreductase;

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005341  34 LANRVAVVTGSTSGIGFAIARRLARDGAHVVISSRKQQNVDRAMAKLQ--GEGLSVAGIVCHVGKAEDREQLVAKALEHC 111
Cdd:PRK07063   5 LAGKVALVTGAAQGIGAAIARAFAREGAAVALADLDAALAERAAAAIArdVAGARVLAVPADVTDAASVAAAVAAAEEAF 84

                         90       100
                 ....*....|....*....|....*....
gi 974005341 112 GGVDFLVCSAGVNpLVGSTLGTSEQIWDK 140
Cdd:PRK07063  85 GPLDVLVNNAGIN-VFADPLAMTDEDWRR 112

3-hydroxybutyrate dehydrogenase; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005341  34 LANRVAVVTGSTSGIGFAIARRLARDGAHVVISSRKQQNVDRAMAKLQGEGLSVAGIVCHVGKAEDREQLVAKALEHCGG 113
Cdd:PRK13394   5 LNGKTAVVTGAASGIGKEIALELARAGAAVAIADLNQDGANAVADEINKAGGKAIGVAMDVTNEDAVNAGIDKVAERFGS 84

                         90       100       110
                 ....*....|....*....|....*....|
gi 974005341 114 VDFLVCSAG---VNPLVgstlGTSEQIWDK 140
Cdd:PRK13394  85 VDILVSNAGiqiVNPIE----NYSFADWKK 110

7 alpha-hydroxysteroid dehydrogenase (7 alpha-HSDH), classical (c) SDRs; This bacterial subgroup contains 7 alpha-HSDHs, including Escherichia coli 7 alpha-HSDH. 7 alpha-HSDH, a member of the SDR family, catalyzes the NAD+ -dependent dehydrogenation of a hydroxyl group at position 7 of the steroid skeleton of bile acids. In humans the two primary bile acids are cholic and chenodeoxycholic acids, these are formed from cholesterol in the liver. Escherichia coli 7 alpha-HSDH dehydroxylates these bile acids in the human intestine. Mammalian 7 alpha-HSDH activity has been found in livers. 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 974005341  38 VAVVTGSTSGIGFAIARRLARDGAHVVISSRKQQNVDRAMAKLQGEGLSVAGIVCHVGKAEDREQLVAKALEHCGGVDFL 117
Cdd:cd05365    1 VAIVTGGAAGIGKAIAGTLAKAGASVVIADLKSEGAEAVAAAIQQAGGQAIGLECNVTSEQDLEAVVKATVSQFGGITIL 80

                 ....*
gi 974005341 118 VCSAG 122
Cdd:cd05365   81 VNNAG 85