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 1376476173   1 MCNNAGIINEK----------HWEKTIAINLGGVVRGTYLALEYMKKENGGSGGVIVNVASMAGLGPLPVAPIYTATKHG 70
Cdd:cd05323    81 LINNAGILDEKsylfagklppPWEKTIDVNLTGVINTTYLALHYMDKNKGGKGGVIVNIGSVAGLYPAPQFPVYSASKHG 160

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1376476173  71 VVGFSRAMAVVSKfSNYGVRINVLCPWFVKTSLLSLLNSEEhtgsfsqmkeitEMLMESEGCLEVDVVAKAFLVLVKDES 150
Cdd:cd05323   161 VVGFTRSLADLLE-YKTGVRVNAICPGFTNTPLLPDLVAKE------------AEMLPSAPTQSPEVVAKAIVYLIEDDE 227

                         170
                  ....*....|....*..
gi 1376476173 151 KDGEALMINPDGAAIIT 167
Cdd:cd05323   228 KNGAIWIVDGGKLIEIE 244

insect type alcohol dehydrogenase (ADH)-like, classical (c) SDRs; This subgroup contains insect type ADH, and 15-hydroxyprostaglandin dehydrogenase (15-PGDH) type I; these proteins are classical SDRs. ADH catalyzes the NAD+-dependent oxidation of alcohols to aldehydes/ketones. This subgroup is distinct from the zinc-dependent alcohol dehydrogenases of the medium chain dehydrogenase/reductase family, and evolved in fruit flies to allow the digestion of fermenting fruit. 15-PGDH catalyzes the NAD-dependent interconversion of (5Z,13E)-(15S)-11alpha,15-dihydroxy-9-oxoprost-13-enoate and (5Z,13E)-11alpha-hydroxy-9,15-dioxoprost-13-enoate, and has a typical SDR glycine-rich NAD-binding motif, which is not fully present in ADH. 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 1376476173   1 MCNNAGIINEK----------HWEKTIAINLGGVVRGTYLALEYMKKENGGSGGVIVNVASMAGLGPLPVAPIYTATKHG 70
Cdd:cd05323    81 LINNAGILDEKsylfagklppPWEKTIDVNLTGVINTTYLALHYMDKNKGGKGGVIVNIGSVAGLYPAPQFPVYSASKHG 160

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1376476173  71 VVGFSRAMAVVSKfSNYGVRINVLCPWFVKTSLLSLLNSEEhtgsfsqmkeitEMLMESEGCLEVDVVAKAFLVLVKDES 150
Cdd:cd05323   161 VVGFTRSLADLLE-YKTGVRVNAICPGFTNTPLLPDLVAKE------------AEMLPSAPTQSPEVVAKAIVYLIEDDE 227

                         170
                  ....*....|....*..
gi 1376476173 151 KDGEALMINPDGAAIIT 167
Cdd:cd05323   228 KNGAIWIVDGGKLIEIE 244

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 1376476173   3 NNAGI--------INEKHWEKTIAINLGGVVRGTYLALEYMKKENGGSggvIVNVASMAGLGPLPVAPIYTATKHGVVGF 74
Cdd:COG1028    89 NNAGItppgpleeLTEEDWDRVLDVNLKGPFLLTRAALPHMRERGGGR---IVNISSIAGLRGSPGQAAYAASKAAVVGL 165

                          90       100       110
                  ....*....|....*....|....*....|....*...
gi 1376476173  75 SRAMAVvsKFSNYGVRINVLCPWFVKTSLL-SLLNSEE 111
Cdd:COG1028   166 TRSLAL--ELAPRGIRVNAVAPGPIDTPMTrALLGAEE 201

insect type alcohol dehydrogenase (ADH)-like, classical (c) SDRs; This subgroup contains insect type ADH, and 15-hydroxyprostaglandin dehydrogenase (15-PGDH) type I; these proteins are classical SDRs. ADH catalyzes the NAD+-dependent oxidation of alcohols to aldehydes/ketones. This subgroup is distinct from the zinc-dependent alcohol dehydrogenases of the medium chain dehydrogenase/reductase family, and evolved in fruit flies to allow the digestion of fermenting fruit. 15-PGDH catalyzes the NAD-dependent interconversion of (5Z,13E)-(15S)-11alpha,15-dihydroxy-9-oxoprost-13-enoate and (5Z,13E)-11alpha-hydroxy-9,15-dioxoprost-13-enoate, and has a typical SDR glycine-rich NAD-binding motif, which is not fully present in ADH. 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 1376476173   1 MCNNAGIINEK----------HWEKTIAINLGGVVRGTYLALEYMKKENGGSGGVIVNVASMAGLGPLPVAPIYTATKHG 70
Cdd:cd05323    81 LINNAGILDEKsylfagklppPWEKTIDVNLTGVINTTYLALHYMDKNKGGKGGVIVNIGSVAGLYPAPQFPVYSASKHG 160

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1376476173  71 VVGFSRAMAVVSKfSNYGVRINVLCPWFVKTSLLSLLNSEEhtgsfsqmkeitEMLMESEGCLEVDVVAKAFLVLVKDES 150
Cdd:cd05323   161 VVGFTRSLADLLE-YKTGVRVNAICPGFTNTPLLPDLVAKE------------AEMLPSAPTQSPEVVAKAIVYLIEDDE 227

                         170
                  ....*....|....*..
gi 1376476173 151 KDGEALMINPDGAAIIT 167
Cdd:cd05323   228 KNGAIWIVDGGKLIEIE 244

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1376476173   3 NNAGI--------INEKHWEKTIAINLGGVVRGTYLALEYMKKENGGSggvIVNVASMAGLGPLPVAPIYTATKHGVVGF 74
Cdd:cd05233    80 NNAGIarpgpleeLTDEDWDRVLDVNLTGVFLLTRAALPHMKKQGGGR---IVNISSVAGLRPLPGQAAYAASKAALEGL 156

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1376476173  75 SRAMAVvsKFSNYGVRINVLCPWFVKTSLLsllnseeHTGSFSQMKEITEMLMESEGCLEVDVVAKAFLVLVKDESK 151
Cdd:cd05233   157 TRSLAL--ELAPYGIRVNAVAPGLVDTPML-------AKLGPEEAEKELAAAIPLGRLGTPEEVAEAVVFLASDEAS 224

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 1376476173   3 NNAGI--------INEKHWEKTIAINLGGVVRGTYLALEYMKKENGGsggVIVNVASMAGLGPLPVAPIYTATKHGVVGF 74
Cdd:COG4221    85 NNAGVallgpleeLDPEDWDRMIDVNVKGVLYVTRAALPAMRARGSG---HIVNISSIAGLRPYPGGAVYAATKAAVRGL 161

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1376476173  75 SRAMAVvsKFSNYGVRINVLCPWFVKTSLLSllnseehtGSFSQMKEITEMLMESEGCLEVDVVAKAFL 143
Cdd:COG4221   162 SESLRA--ELRPTGIRVTVIEPGAVDTEFLD--------SVFDGDAEAAAAVYEGLEPLTPEDVAEAVL 220

SDR family oxidoreductase;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1376476173   3 NNAGI-----INE---KHWEKTIAINLGGVVRGTYLALEYMKKENGGSggvIVNVASMAGLGPLPVAPIYTATKHGVVGF 74
Cdd:PRK05650   83 NNAGVasggfFEElslEDWDWQIAINLMGVVKGCKAFLPLFKRQKSGR---IVNIASMAGLMQGPAMSSYNVAKAGVVAL 159

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1376476173  75 SRAMAVvsKFSNYGVRINVLCPWFVKTSLLSLLNSEEHTgsfsqMKEITEMLMESE--------GCLEVDVVAKAFLVLV 146
Cdd:PRK05650  160 SETLLV--ELADDEIGVHVVCPSFFQTNLLDSFRGPNPA-----MKAQVGKLLEKSpitaadiaDYIYQQVAKGEFLILP 232

                  ....*
gi 1376476173 147 KDESK 151
Cdd:PRK05650  233 HEQGR 237

3beta17beta hydroxysteroid dehydrogenase-like, classical (c) SDRs; This subgroup includes members identified as 3beta17beta hydroxysteroid dehydrogenase, 20beta hydroxysteroid dehydrogenase, and R-alcohol dehydrogenase. These proteins exhibit the canonical active site tetrad and glycine rich NAD(P)-binding motif of the classical SDRs. 17beta-dehydrogenases are a group of isozymes that catalyze activation and inactivation of estrogen and androgens, and include members of the SDR family. 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 1376476173   3 NNAGIINEK--------HWEKTIAINLGGVVRGTYLALEYMKKENGGSggvIVNVASMAGLGPLPVAPIYTATKHGVVGF 74
Cdd:cd05341    85 NNAGILTGGtvetttleEWRRLLDINLTGVFLGTRAVIPPMKEAGGGS---IINMSSIEGLVGDPALAAYNASKGAVRGL 161

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1376476173  75 SRAMAVVSKFSNYGVRINVLCPWFVKTSLLsllnsEEHTGSFSQMKEITEMLMESEGclEVDVVAKAFLVLVKDESK 151
Cdd:cd05341   162 TKSAALECATQGYGIRVNSVHPGYIYTPMT-----DELLIAQGEMGNYPNTPMGRAG--EPDEIAYAVVYLASDESS 231

SDR family oxidoreductase;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1376476173   2 CNNAGII---------NEKHWEKTIAINlggvVRGTYLALEY----MKKENGGSggvIVNVASMAGLGPLPVAPIYTATK 68
Cdd:PRK06172   89 FNNAGIEieqgrlaegSEAEFDAIMGVN----VKGVWLCMKYqiplMLAQGGGA---IVNTASVAGLGAAPKMSIYAASK 161

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1376476173  69 HGVVGFSRAMAVvsKFSNYGVRINVLCPWFVKTSLLsllnsEEHTGSFSQMKEITEMLMESEGCLEVDVVAKAFLVLVKD 148
Cdd:PRK06172  162 HAVIGLTKSAAI--EYAKKGIRVNAVCPAVIDTDMF-----RRAYEADPRKAEFAAAMHPVGRIGKVEEVASAVLYLCSD 234

                         170
                  ....*....|....*....
gi 1376476173 149 ESK--DGEALMInpDGAAI 165
Cdd:PRK06172  235 GASftTGHALMV--DGGAT 251

short chain dehydrogenase; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1376476173   3 NNAGII--------NEKHWEKTIAINLGGVVRGTYLALEYMKKEngGSGGvIVNVASMAGLGPLPVAPIYTATKHGVVGF 74
Cdd:PRK07825   84 NNAGVMpvgpfldePDAVTRRILDVNVYGVILGSKLAAPRMVPR--GRGH-VVNVASLAGKIPVPGMATYCASKHAVVGF 160

                          90       100       110
                  ....*....|....*....|....*....|.
gi 1376476173  75 SRAMAVvsKFSNYGVRINVLCPWFVKTSLLS 105
Cdd:PRK07825  161 TDAARL--ELRGTGVHVSVVLPSFVNTELIA 189

SDR family oxidoreductase;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1376476173   1 MCNNAGIINEKHWE--------KTIAINLGGVVRGTYLALEYMKKEnggSGGVIVNVASMAGLGPLPVAPIYTATKHGVV 72
Cdd:PRK08267   81 LFNNAGILRGGPFEdipleahdRVIDINVKGVLNGAHAALPYLKAT---PGARVINTSSASAIYGQPGLAVYSATKFAVR 157

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|...
gi 1376476173  73 GFSRAMAVvsKFSNYGVRINVLCPWFVKTSLLSLLNSEEHTGS 115
Cdd:PRK08267  158 GLTEALDL--EWRRHGIRVADVMPLFVDTAMLDGTSNEVDAGS 198

secoisolariciresinol dehydrogenase (secoisolariciresinol-DH)-like, classical (c) SDRs; Podophyllum secoisolariciresinol-DH is a homo tetrameric, classical SDR that catalyzes the NAD-dependent conversion of (-)-secoisolariciresinol to (-)-matairesinol via a (-)-lactol intermediate. (-)-Matairesinol is an intermediate to various 8'-lignans, including the cancer-preventive mammalian lignan, and those involved in vascular plant defense. This subgroup also includes rice momilactone A synthase which catalyzes the conversion of 3beta-hydroxy-9betaH-pimara-7,15-dien-19,6beta-olide into momilactone A, Arabidopsis ABA2 which during abscisic acid (ABA) biosynthesis, catalyzes the conversion of xanthoxin to abscisic aldehyde and, maize Tasselseed2 which participate in the maize sex determination pathway. 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 1376476173   1 MCNNAGII----------NEKHWEKTIAINLGGVVRGTYLALEYMKKENGGSggvIVNVAS----MAGLGPLPvapiYTA 66
Cdd:cd05326    83 MFNNAGVLgapcysiletSLEEFERVLDVNVYGAFLGTKHAARVMIPAKKGS---IVSVASvagvVGGLGPHA----YTA 155

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1376476173  67 TKHGVVGFSRAMAvvSKFSNYGVRINVLCPWFVKTSLLsllnseehTGSFSQMKEITEMLMESE-----GCLEVDVVAKA 141
Cdd:cd05326   156 SKHAVLGLTRSAA--TELGEHGIRVNCVSPYGVATPLL--------TAGFGVEDEAIEEAVRGAanlkgTALRPEDIAAA 225

                         170       180
                  ....*....|....*....|
gi 1376476173 142 FLVLVKDESK--DGEALMIN 159
Cdd:cd05326   226 VLYLASDDSRyvSGQNLVVD 245

HetN oxidoreductase-like, classical (c) SDR; This subgroup includes Anabaena sp. strain PCC 7120 HetN, a putative oxidoreductase involved in heterocyst differentiation, and related proteins. 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 1376476173   1 MCNNAGI--------INEKHWEKTIAINLGGVVRGTYLALEYMKKEngGSGGvIVNVASMAGLGPLPVAPIYTATKHGVV 72
Cdd:cd08932    77 LVHNAGIgrpttlreGSDAELEAHFSINVIAPAELTRALLPALREA--GSGR-VVFLNSLSGKRVLAGNAGYSASKFALR 153

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1376476173  73 GFSRAMAVVskFSNYGVRINVLCPWFVKTSLLSLLNSEEHT--GSFSQMKEITE---MLME-SEGCLEVDVV 138
Cdd:cd08932   154 ALAHALRQE--GWDHGVRVSAVCPGFVDTPMAQGLTLVGAFppEEMIQPKDIANlvrMVIElPENITSVAVL 223

d-3-hydroxybutyrate dehydrogenase (HBDH), classical (c) SDRs; DHBDH, an NAD+ -dependent enzyme, catalyzes the interconversion of D-3-hydroxybutyrate and acetoacetate. It is a classical SDR, with the canonical NAD-binding motif and active site tetrad. 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 1376476173   3 NNAGI--------INEKHWEKTIAINLGGVVRGTYLALEYMKKENGGSggvIVNVASMAGLGPLPVAPIYTATKHGVVGF 74
Cdd:cd08940    87 NNAGIqhvapiedFPTEKWDAIIALNLSAVFHTTRLALPHMKKQGWGR---IINIASVHGLVASANKSAYVAAKHGVVGL 163

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1376476173  75 SRAMAVvsKFSNYGVRINVLCPWFVKTSL----LSLLNSEEHTGSFSQMKEITEMLMESEGCLEVDVVAKAFLVLVKDES 150
Cdd:cd08940   164 TKVVAL--ETAGTGVTCNAICPGWVLTPLvekqISALAQKNGVPQEQAARELLLEKQPSKQFVTPEQLGDTAVFLASDAA 241

                         170
                  ....*....|..
gi 1376476173 151 KDGEALMINPDG 162
Cdd:cd08940   242 SQITGTAVSVDG 253

SDR family oxidoreductase;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1376476173   3 NNAGI--------INEKHWEKTIAINLGGVVRGTYLALEYMKKEngGSGGVIVNVASMAGLGPLPVAPIYTATKHGVVGF 74
Cdd:PRK05855  398 NNAGIgmaggfldTSAEDWDRVLDVNLWGVIHGCRLFGRQMVER--GTGGHIVNVASAAAYAPSRSLPAYATSKAAVLML 475

                          90       100       110
                  ....*....|....*....|....*....|
gi 1376476173  75 S---RAmavvsKFSNYGVRINVLCPWFVKT 101
Cdd:PRK05855  476 SeclRA-----ELAAAGIGVTAICPGFVDT 500

short chain dehydrogenase; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1376476173   1 MCNNAGI---------INEKHWEKTIAINLGGVVRGTYLALEYMKKenGGSGGVIVNVASMAGLGPLPVAPIYTATKHGV 71
Cdd:PRK12829   90 LVNNAGIagptggideITPEQWEQTLAVNLNGQFYFARAAVPLLKA--SGHGGVIIALSSVAGRLGYPGRTPYAASKWAV 167

                          90       100       110
                  ....*....|....*....|....*....|
gi 1376476173  72 VGFSRAMAvvSKFSNYGVRINVLCPWFVKT 101
Cdd:PRK12829  168 VGLVKSLA--IELGPLGIRVNAILPGIVRG 195

2-dehydro-3-deoxy-D-gluconate 5-dehydrogenase KduD;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1376476173   3 NNAGII--------NEKHWEKTIAINLGGVVRGTYLALEYMKKENGGSggvIVNVASMAGLGPLPVAPIYTATKHGVVGF 74
Cdd:PRK06935   97 NNAGTIrraplleyKDEDWNAVMDINLNSVYHLSQAVAKVMAKQGSGK---IINIASMLSFQGGKFVPAYTASKHGVAGL 173

                          90       100
                  ....*....|....*....|....*..
gi 1376476173  75 SRAMAvvSKFSNYGVRINVLCPWFVKT 101
Cdd:PRK06935  174 TKAFA--NELAAYNIQVNAIAPGYIKT 198

hypothetical protein; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1376476173   1 MCNNAGI--------INEKHWEKTIAINLGGVVRG----TYLALEYMKKENGGSGGvIVNVASMAGLGPLPVAPIYTATK 68
Cdd:PRK06194   87 LFNNAGVgagglvweNSLADWEWVLGVNLWGVIHGvrafTPLMLAAAEKDPAYEGH-IVNTASMAGLLAPPAMGIYNVSK 165

                          90       100       110
                  ....*....|....*....|....*....|....*
gi 1376476173  69 HGVVGFSRAMAVVSKFSNYGVRINVLCPWFVKTSL 103
Cdd:PRK06194  166 HAVVSLTETLYQDLSLVTDQVGASVLCPYFVPTGI 200

short chain dehydrogenase; Validated

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1376476173   3 NNAGI--------INEKHWEKTIAINLGGVVRGTYLALEYMKKENGGSggvIVNVASMAGLGPLPVAPIYTATKHGVVGF 74
Cdd:PRK07069   85 NNAGVgsfgaieqIELDEWRRVMAINVESIFLGCKHALPYLRASQPAS---IVNISSVAAFKAEPDYTAYNASKAAVASL 161

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1376476173  75 SRAMAVVSKFSNYGVRINVLCPWFVKTSLLsllnseehTGSFSQM--KEITEML-----MESEGclEVDVVAKAFLVLVK 147
Cdd:PRK07069  162 TKSIALDCARRGLDVRCNSIHPTFIRTGIV--------DPIFQRLgeEEATRKLargvpLGRLG--EPDDVAHAVLYLAS 231

                  ....
gi 1376476173 148 DESK 151
Cdd:PRK07069  232 DESR 235

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1376476173   3 NNAGI--------INEKHWEKTIAINLGGVVRGTYLALEYMKKenggsGGVIVNVASMAGLGPLPVAPIYTATKHGVVGF 74
Cdd:PRK06077   90 NNAGLglfspflnVDDKLIDKHISTDFKSVIYCSQELAKEMRE-----GGAIVNIASVAGIRPAYGLSIYGAMKAAVINL 164

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1376476173  75 SRAMAVVSKFSnygVRINVLCPWFVKT----SLLSLLNSEEhtGSFSQMKEITEMLMESEGclevdvVAKAFLVLVKDES 150
Cdd:PRK06077  165 TKYLALELAPK---IRVNAIAPGFVKTklgeSLFKVLGMSE--KEFAEKFTLMGKILDPEE------VAEFVAAILKIES 233

                  ....*....
gi 1376476173 151 KDGEALMIN 159
Cdd:PRK06077  234 ITGQVFVLD 242

3-oxoacyl-ACP reductase;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1376476173   3 NNAGI--------INEKHWEKTIAINLGGVVRGTYLALEYMKKENGGSggvIVNVASMAGLGPLPVAPIYTATKHGVVGF 74
Cdd:PRK12824   86 NNAGItrdsvfkrMSHQEWNDVINTNLNSVFNVTQPLFAAMCEQGYGR---IINISSVNGLKGQFGQTNYSAAKAGMIGF 162

                          90       100       110
                  ....*....|....*....|....*....|....*.
gi 1376476173  75 SRAMAvvSKFSNYGVRINVLCPWFVKTSLLSLLNSE 110
Cdd:PRK12824  163 TKALA--SEGARYGITVNCIAPGYIATPMVEQMGPE 196

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1376476173   3 NNAGII--------NEKHWEKTIAINLGGVVRGTYLALEYMKKENGGSggvIVNVASMAGLGPLPVAPIYTATKHGVVGF 74
Cdd:PRK12825   90 NNAGIFedkpladmSDDEWDEVIDVNLSGVFHLLRAVVPPMRKQRGGR---IVNISSVAGLPGWPGRSNYAAAKAGLVGL 166

                          90       100
                  ....*....|....*....|....*..
gi 1376476173  75 SRAMAVvsKFSNYGVRINVLCPWFVKT 101
Cdd:PRK12825  167 TKALAR--ELAEYGITVNMVAPGDIDT 191

SDR family oxidoreductase;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1376476173   3 NNAGI--------INEKHWEKTIAINLGGVVRGTYLALEYMKKenGGSGGVIVNVASMAGLGPLPVAPIYTATKHGVVGF 74
Cdd:PRK07832   84 NIAGIsawgtvdrLTHEQWRRMVDVNLMGPIHVIETFVPPMVA--AGRGGHLVNVSSAAGLVALPWHAAYSASKFGLRGL 161

                          90       100       110
                  ....*....|....*....|....*....|..
gi 1376476173  75 SRamavVSKF--SNYGVRINVLCPWFVKTSLL 104
Cdd:PRK07832  162 SE----VLRFdlARHGIGVSVVVPGAVKTPLV 189