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 966921443   2 RKVVLITGASSGIGLALCKRLLAEDD---ELHLCLACRNRNKAEAVRASLLASHPTAEVT--IVQVDISNLQSVFRASKE 76
Cdd:cd08941    1 RKVVLVTGANSGLGLAICERLLAEDDenpELTLILACRNLQRAEAACRALLASHPDARVVfdYVLVDLSNMVSVFAAAKE 80

                         90       100       110
                 ....*....|....*....|....*....|....*....
gi 966921443  77 LKQRFQRLDCIYLNAGIMPNPQLN-----IKALFFGLFS 110
Cdd:cd08941   81 LKKRYPRLDYLYLNAGIMPNPGIDwigaiKEVLTNPLFA 119

3-keto steroid reductase, classical (c) SDRs; 3-keto steroid reductase (in concert with other enzymes) catalyzes NADP-dependent sterol C-4 demethylation, as part of steroid biosynthesis. 3-keto reductase is a classical SDR, with a well conserved canonical active site tetrad and fairly well conserved characteristic 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 966921443   2 RKVVLITGASSGIGLALCKRLLAEDD---ELHLCLACRNRNKAEAVRASLLASHPTAEVT--IVQVDISNLQSVFRASKE 76
Cdd:cd08941    1 RKVVLVTGANSGLGLAICERLLAEDDenpELTLILACRNLQRAEAACRALLASHPDARVVfdYVLVDLSNMVSVFAAAKE 80

                         90       100       110
                 ....*....|....*....|....*....|....*....
gi 966921443  77 LKQRFQRLDCIYLNAGIMPNPQLN-----IKALFFGLFS 110
Cdd:cd08941   81 LKKRYPRLDYLYLNAGIMPNPGIDwigaiKEVLTNPLFA 119

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966921443    3 KVVLITGASSGIGLALCKRLLAEDDELHLCLacRNRNKAEAVRASLLASHPtaEVTIVQVDISNLQSVFRASKELKQRFQ 82
Cdd:pfam00106   1 KVALVTGASSGIGRAIAKRLAKEGAKVVLVD--RSEEKLEAVAKELGALGG--KALFIQGDVTDRAQVKALVEQAVERLG 76

                          90       100       110
                  ....*....|....*....|....*....|....*....
gi 966921443   83 RLDCIYLNAGIMPNP--------------QLNIKALFFG 107
Cdd:pfam00106  77 RLDILVNNAGITGLGpfselsdedwerviDVNLTGVFNL 115

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 966921443     3 KVVLITGASSGIGLALCkRLLAEDDELHLCLACRNRNKAEAVRASL--LASHpTAEVTIVQVDISNLQSVFRASKELKQR 80
Cdd:smart00822   1 GTYLITGGLGGLGRALA-RWLAERGARRLVLLSRSGPDAPGAAALLaeLEAA-GARVTVVACDVADRDALAAVLAAIPAV 78

                           90
                   ....*....|...
gi 966921443    81 FQRLDCIYLNAGI 93
Cdd:smart00822  79 EGPLTGVIHAAGV 91

3-keto steroid reductase, classical (c) SDRs; 3-keto steroid reductase (in concert with other enzymes) catalyzes NADP-dependent sterol C-4 demethylation, as part of steroid biosynthesis. 3-keto reductase is a classical SDR, with a well conserved canonical active site tetrad and fairly well conserved characteristic 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 966921443   2 RKVVLITGASSGIGLALCKRLLAEDD---ELHLCLACRNRNKAEAVRASLLASHPTAEVT--IVQVDISNLQSVFRASKE 76
Cdd:cd08941    1 RKVVLVTGANSGLGLAICERLLAEDDenpELTLILACRNLQRAEAACRALLASHPDARVVfdYVLVDLSNMVSVFAAAKE 80

                         90       100       110
                 ....*....|....*....|....*....|....*....
gi 966921443  77 LKQRFQRLDCIYLNAGIMPNPQLN-----IKALFFGLFS 110
Cdd:cd08941   81 LKKRYPRLDYLYLNAGIMPNPGIDwigaiKEVLTNPLFA 119

Short-chain dehydrogenase [General function prediction only];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966921443   1 MRKVVLITGASSGIGLALCKRLLAEDDelHLCLACRNRNKAEAVRASLLASHptAEVTIVQVDISNLQSVFRASKELKQR 80
Cdd:COG0300    4 TGKTVLITGASSGIGRALARALAARGA--RVVLVARDAERLEALAAELRAAG--ARVEVVALDVTDPDAVAALAEAVLAR 79

                         90
                 ....*....|....*
gi 966921443  81 FQRLDCIYLNAGIMP 95
Cdd:COG0300   80 FGPIDVLVNNAGVGG 94

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 966921443   3 KVVLITGASSGIGLALCKRLLAEDDeLHLCLACRNRNKAEAVRASLLASHPTAEVtiVQVDISNLQSVFRASKELKQRFQ 82
Cdd:cd05324    1 KVALVTGANRGIGFEIVRQLAKSGP-GTVILTARDVERGQAAVEKLRAEGLSVRF--HQLDVTDDASIEAAADFVEEKYG 77

                         90
                 ....*....|..
gi 966921443  83 RLDCIYLNAGIM 94
Cdd:cd05324   78 GLDILVNNAGIA 89

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 966921443   5 VLITGASSGIGLALCKRLLAEDDelHLCLACRNRNKAEAVRASLLAShptAEVTIVQVDISNLQSVFRASKELKQRFQRL 84
Cdd:cd05233    1 ALVTGASSGIGRAIARRLAREGA--KVVLADRNEEALAELAAIEALG---GNAVAVQADVSDEEDVEALVEEALEEFGRL 75

                         90
                 ....*....|....*
gi 966921443  85 DCIYLNAGIMPNPQL 99
Cdd:cd05233   76 DILVNNAGIARPGPL 90

short chain dehydrogenase; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966921443   3 KVVLITGASSGIGLAlCKRLLAEDDElHLCLACRNRNKAEAVRASLLASHPTAEVTIVQVDISNLQSVFRASKELKQRFQ 82
Cdd:PRK06197  17 RVAVVTGANTGLGYE-TAAALAAKGA-HVVLAVRNLDKGKAAAARITAATPGADVTLQELDLTSLASVRAAADALRAAYP 94

                         90
                 ....*....|....*.
gi 966921443  83 RLDCIYLNAGIMPNPQ 98
Cdd:PRK06197  95 RIDLLINNAGVMYTPK 110

17beta hydroxysteroid dehydrogenase-like, classical (c) SDRs; 17beta-hydroxysteroid dehydrogenases are a group of isozymes that catalyze activation and inactivation of estrogen and androgens. 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 966921443   3 KVVLITGASSGIGLALCKRLLAEDDELHLClaCRNRNKAEAVRASLLAShptaeVTIVQVDISNLQSVFRASKELKQRFQ 82
Cdd:cd05374    1 KVVLITGCSSGIGLALALALAAQGYRVIAT--ARNPDKLESLGELLNDN-----LEVLELDVTDEESIKAAVKEVIERFG 73

                         90
                 ....*....|..
gi 966921443  83 RLDCIYLNAGIM 94
Cdd:cd05374   74 RIDVLVNNAGYG 85

light-dependent protochlorophyllide reductase (LPOR)-like, classical (c)-like SDRs; Classical SDR-like subgroup containing LPOR and related proteins. Protochlorophyllide (Pchlide) reductases act in chlorophyll biosynthesis. There are distinct enzymes that catalyze Pchlide reduction in light or dark conditions. Light-dependent reduction is via an NADP-dependent SDR, LPOR. Proteins in this subfamily share the glycine-rich NAD-binding motif of the classical SDRs, have a partial match to the canonical active site tetrad, but lack the typical active site Ser. 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 966921443   2 RKVVLITGASSGIGLAlCKRLLAEDDELHLCLACRNRNKAEAVRASLlaSHPTAEVTIVQVDISNLQSVFRASKELKQRF 81
Cdd:cd09810    1 KGTVVITGASSGLGLA-AAKALARRGEWHVVMACRDFLKAEQAAQEV--GMPKDSYSVLHCDLASLDSVRQFVDNFRRTG 77

                         90
                 ....*....|..
gi 966921443  82 QRLDCIYLNAGI 93
Cdd:cd09810   78 RPLDALVCNAAV 89

SDR family oxidoreductase;

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966921443   3 KVVLITGASSGIGLALCKRLLAEDDElhLCLACRNRNKAEAVRASLLASHPTAEVTIVQVDISNLQSVFRASKELKQRFQ 82
Cdd:PRK05854  15 KRAVVTGASDGLGLGLARRLAAAGAE--VILPVRNRAKGEAAVAAIRTAVPDAKLSLRALDLSSLASVAALGEQLRAEGR 92

                         90
                 ....*....|....*.
gi 966921443  83 RLDCIYLNAGIMPNPQ 98
Cdd:PRK05854  93 PIHLLINNAGVMTPPE 108

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 966921443   3 KVVLITGASSGIGLALCKRLLAEDDELHLClacrnrNKAEAVRASLLASHPTAEvtIVQVDISNLQSVFRASKELKQRFQ 82
Cdd:cd05370    6 NTVLITGGTSGIGLALARKFLEAGNTVIIT------GRREERLAEAKKELPNIH--TIVLDVGDAESVEALAEALLSEYP 77

                         90
                 ....*....|..
gi 966921443  83 RLDCIYLNAGIM 94
Cdd:cd05370   78 NLDILINNAGIQ 89

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966921443   1 MRKVVLITGASSGIGLALCKRLLAEDDelHLCLACR-NRNKAEAVRASLLASHPTAEVtiVQVDISNLQSVFRASKELKQ 79
Cdd:PRK12825   5 MGRVALVTGAARGLGRAIALRLARAGA--DVVVHYRsDEEAAEELVEAVEALGRRAQA--VQADVTDKAALEAAVAAAVE 80

                         90
                 ....*....|....
gi 966921443  80 RFQRLDCIYLNAGI 93
Cdd:PRK12825  81 RFGRIDILVNNAGI 94

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 966921443   3 KVVLITGASSGIGLALCKRLLAEDDelHLCLACRNRNKAEAvrASLLASHPTAEVTIVQVDISNLQSVFRASKELKQRFQ 82
Cdd:cd05333    1 KVALVTGASRGIGRAIALRLAAEGA--KVAVTDRSEEAAAE--TVEEIKALGGNAAALEADVSDREAVEALVEKVEAEFG 76

                         90
                 ....*....|.
gi 966921443  83 RLDCIYLNAGI 93
Cdd:cd05333   77 PVDILVNNAGI 87

classical (c) SDR, subgroup 5; These proteins are members of the classical SDR family, with a canonical active site tetrad and a typical Gly-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 966921443   3 KVVLITGASSGIGLALCKRLLAEDDelHLCLACRNRNKAEAVRASLLASHPTaEVTIVQVDISNLQSVFRASKELKQRFQ 82
Cdd:cd05346    1 KTVLITGASSGIGEATARRFAKAGA--KLILTGRRAERLQELADELGAKFPV-KVLPLQLDVSDRESIEAALENLPEEFR 77

                         90
                 ....*....|
gi 966921443  83 RLDCIYLNAG 92
Cdd:cd05346   78 DIDILVNNAG 87

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966921443   3 KVVLITGASSGIGLALCKRLLAEDDelHLCLACRNRNKAEAVRASLLASH--PTAEVTIVQVDISNLQSVFRASKELKQR 80
Cdd:cd08939    2 KHVLITGGSSGIGKALAKELVKEGA--NVIIVARSESKLEEAVEEIEAEAnaSGQKVSYISADLSDYEEVEQAFAQAVEK 79

                         90
                 ....*....|...
gi 966921443  81 FQRLDCIYLNAGI 93
Cdd:cd08939   80 GGPPDLVVNCAGI 92

cyclohexanol reductases, including levodione reductase, classical (c) SDRs; Cyloclohexanol reductases,including (6R)-2,2,6-trimethyl-1,4-cyclohexanedione (levodione) reductase of Corynebacterium aquaticum, catalyze the reversible oxidoreduction of hydroxycyclohexanone derivatives. 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 966921443   3 KVVLITGASSGIGLALCKRLLAEDDELhlCLACRNRNKAEAVRASLLASHPTAEVTIVQVDISNLQSVFRASKELKQRFQ 82
Cdd:cd05330    4 KVVLITGGGSGLGLATAVRLAKEGAKL--SLVDLNEEGLEAAKAALLEIAPDAEVLLIKADVSDEAQVEAYVDATVEQFG 81

                         90
                 ....*....|.
gi 966921443  83 RLDCIYLNAGI 93
Cdd:cd05330   82 RIDGFFNNAGI 92

11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1)-like, classical (c) SDRs; Human 11beta_HSD1 catalyzes the NADP(H)-dependent interconversion of cortisone and cortisol. This subgroup also includes human dehydrogenase/reductase SDR family member 7C (DHRS7C) and DHRS7B. These proteins have the GxxxGxG nucleotide binding motif and S-Y-K catalytic triad characteristic of the SDRs, but have an atypical C-terminal domain that contributes to homodimerization contacts. 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 966921443   3 KVVLITGASSGIGLALCKRLLAEDdeLHLCLACRNRNKAEAVrASLLASHPTAEVTIVQVDISNLQSVFRASKELKQRFQ 82
Cdd:cd05332    4 KVVIITGASSGIGEELAYHLARLG--ARLVLSARREERLEEV-KSECLELGAPSPHVVPLDMSDLEDAEQVVEEALKLFG 80

                         90
                 ....*....|.
gi 966921443  83 RLDCIYLNAGI 93
Cdd:cd05332   81 GLDILINNAGI 91

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 966921443   3 KVVLITGASSGIGLALCKRLLAEDDELHLClaCRNRNKAEAVRASLlaSHPTAEVTIVQVDISNLQSVFRASKELKQRFQ 82
Cdd:cd05344    2 KVALVTAASSGIGLAIARALAREGARVAIC--ARNRENLERAASEL--RAGGAGVLAVVADLTDPEDIDRLVEKAGDAFG 77

                         90
                 ....*....|
gi 966921443  83 RLDCIYLNAG 92
Cdd:cd05344   78 RVDILVNNAG 87

SDR family oxidoreductase;

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966921443   1 MRKVVLITGASSGIGLALCKRLLAEDdelHLCLAC-RNRNKAEAVRASLLASHPTAEVTIVQVDISNLQSVFRASKELKq 79
Cdd:PRK06914   2 NKKIAIVTGASSGFGLLTTLELAKKG---YLVIATmRNPEKQENLLSQATQLNLQQNIKVQQLDVTDQNSIHNFQLVLK- 77

                         90
                 ....*....|...
gi 966921443  80 RFQRLDCIYLNAG 92
Cdd:PRK06914  78 EIGRIDLLVNNAG 90

SDR family oxidoreductase;

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966921443   3 KVVLITGASSGIGLALCKRLLAEDDELHLClaCRNRNKAEAVRASLLASHptaEVTIVQVDISNLQSVFRASKELKQRFQ 82
Cdd:PRK07326   7 KVALITGGSKGIGFAIAEALLAEGYKVAIT--ARDQKELEEAAAELNNKG---NVLGLAADVRDEADVQRAVDAIVAAFG 81

                         90
                 ....*....|.
gi 966921443  83 RLDCIYLNAGI 93
Cdd:PRK07326  82 GLDVLIANAGV 92

classical (c) SDR, subgroup 6; These proteins are members of the classical SDR family, with a canonical active site tetrad and a fairly well conserved typical Gly-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 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 966921443   5 VLITGASSGIGLALCKRLLAEDdeLHLCLACRNRNKAEAVRASLLAshPTAEVTIVQVDISNLQSVFRASKELKQRFQRL 84
Cdd:cd05350    1 VLITGASSGIGRALAREFAKAG--YNVALAARRTDRLDELKAELLN--PNPSVEVEILDVTDEERNQLVIAELEAELGGL 76

                 ....*....
gi 966921443  85 DCIYLNAGI 93
Cdd:cd05350   77 DLVIINAGV 85

SDR family oxidoreductase;

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966921443   1 MRKVVLITGASSGIGLALCkrLLAEDDELHLCLA-CRNRNKAEAVRASLLASHPTAevTIVQVDISNLQSVFRASKELKQ 79
Cdd:PRK06123   1 MRKVMIITGASRGIGAATA--LLAAERGYAVCLNyLRNRDAAEAVVQAIRRQGGEA--LAVAADVADEADVLRLFEAVDR 76

                         90
                 ....*....|....*
gi 966921443  80 RFQRLDCIYLNAGIM 94
Cdd:PRK06123  77 ELGRLDALVNNAGIL 91

human WWOX (WW domain-containing oxidoreductase)-like, classical (c)-like SDRs; Classical-like SDR domain of human WWOX and related proteins. Proteins in this subfamily share the glycine-rich NAD-binding motif of the classical SDRs, have a partial match to the canonical active site tetrad, but lack the typical active site Ser. 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 966921443   3 KVVLITGASSGIGLALCKRLLAEDdeLHLCLACRNRNKAEAVRASLLASHPTAEVTIVQVDISNLQSVFRASKELKQRFQ 82
Cdd:cd09809    2 KVIIITGANSGIGFETARSFALHG--AHVILACRNMSRASAAVSRILEEWHKARVEAMTLDLASLRSVQRFAEAFKAKNS 79

                         90
                 ....*....|....*
gi 966921443  83 RLDCIYLNAGIMPNP 97
Cdd:cd09809   80 PLHVLVCNAAVFALP 94

short chain dehydrogenase; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966921443   3 KVVLITGASSGIGLAlCKRLLAEDDElHLCLACRNRNKAEaVRASLLASHPTAevtiVQVDISNLQSVFRASKELKQRFQ 82
Cdd:PRK06841  16 KVAVVTGGASGIGHA-IAELFAAKGA-RVALLDRSEDVAE-VAAQLLGGNAKG----LVCDVSDSQSVEAAVAAVISAFG 88

                         90
                 ....*....|...
gi 966921443  83 RLDCIYLNAGIMP 95
Cdd:PRK06841  89 RIDILVNSAGVAL 101

SDR family oxidoreductase;

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966921443   3 KVVLITGASSGIGLALCKRLLAEDDELHLClaCRNRNKAEAVRASLLASHPTAEVTIVQVDISNLQSVFRASKELKQRFQ 82
Cdd:PRK07062   9 RVAVVTGGSSGIGLATVELLLEAGASVAIC--GRDEERLASAEARLREKFPGARLLAARCDVLDEADVAAFAAAVEARFG 86

                         90
                 ....*....|
gi 966921443  83 RLDCIYLNAG 92
Cdd:PRK07062  87 GVDMLVNNAG 96

SDR family oxidoreductase;

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966921443   3 KVVLITGASSGIGLALCKRLLaeDDELHLCLACRNRNKAEAVRAsllashpTAEVTIVQVDISNLQSVfrasKELKQRF- 81
Cdd:PRK08177   2 RTALIIGASRGLGLGLVDRLL--ERGWQVTATVRGPQQDTALQA-------LPGVHIEKLDMNDPASL----DQLLQRLq 68

                         90       100       110
                 ....*....|....*....|....*....|....
gi 966921443  82 -QRLDCIYLNAGIM-PNPQLNIKA-------LFF 106
Cdd:PRK08177  69 gQRFDLLFVNAGISgPAHQSAADAtaaeigqLFL 102

meso-2,3-butanediol dehydrogenase-like, classical (c) SDRs; 2,3-butanediol dehydrogenases (BDHs) catalyze the NAD+ dependent conversion of 2,3-butanediol to acetonin; BDHs are classified into types according to their stereospecificity as to substrates and products. Included in this subgroup are Klebsiella pneumonia meso-BDH which catalyzes meso-2,3-butanediol to D(-)-acetonin, and Corynebacterium glutamicum L-BDH which catalyzes lX+)-2,3-butanediol to L(+)-acetonin. This subgroup is comprised of classical SDRs with the characteristic catalytic triad and 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 966921443   1 MRKVVLITGASSGIGLALCKRLLAedDELHLCLACRNRNKAEAVRASLLASHPTAEVTIVqVDISNLQSVFRASKELKQR 80
Cdd:cd05366    1 MSKVAIITGAAQGIGRAIAERLAA--DGFNIVLADLNLEEAAKSTIQEISEAGYNAVAVG-ADVTDKDDVEALIDQAVEK 77

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|.
gi 966921443  81 FQRLDCIYLNAGIMP-NP-------------QLNIKALFFG 107
Cdd:cd05366   78 FGSFDVMVNNAGIAPiTPlltiteedlkkvyAVNVFGVLFG 118

SDR family oxidoreductase;

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966921443   1 MRKVVLITGASSGIGLALCkRLLAEDDELHLClaCRNrnkAEAVRAsLLASHPTAEVtiVQVDISNLQSVFRASKELKqr 80
Cdd:PRK08219   2 ERPTALITGASRGIGAAIA-RELAPTHTLLLG--GRP---AERLDE-LAAELPGATP--FPVDLTDPEAIAAAVEQLG-- 70

                         90
                 ....*....|...
gi 966921443  81 fqRLDCIYLNAGI 93
Cdd:PRK08219  71 --RLDVLVHNAGV 81

SDR family oxidoreductase;

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966921443   3 KVVLITGASSGIGLALCKRlLAEDDELHLCLAcRNRNKAEAVRASLLASHPTAEVtiVQVDISNLQSVFRASKELKQRFQ 82
Cdd:PRK07201 372 KVVLITGASSGIGRATAIK-VAEAGATVFLVA-RNGEALDELVAEIRAKGGTAHA--YTCDLTDSAAVDHTVKDILAEHG 447

                         90
                 ....*....|
gi 966921443  83 RLDCIYLNAG 92
Cdd:PRK07201 448 HVDYLVNNAG 457