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 228481714   1 GASGAIGGAIAIELVKSGMIVCALSRRRDKVEKLRVSLFDVA-GSLNYVECDITVEDDVKYAFGWIENTYGGVDMLVNNA 79
Cdd:cd05343   13 GASVGIGAAVARALVQHGMKVVGCARRVDKIEALAAECQSAGyPTLFPYQCDLSNEEQILSMFSAIRTQHQGVDVCINNA 92

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 228481714  80 GIITKCLLTEkNNTRDLYKTMETNIIGLSLCTREAVKSMKARDV-KGHIINVNSIFGHKVHQAvpgtrPLNGMYPASKYA 158
Cdd:cd05343   93 GLARPEPLLS-GKTEGWKEMFDVNVLALSICTREAYQSMKERNVdDGHIININSMSGHRVPPV-----SVFHFYAATKHA 166

                 ...
gi 228481714 159 VTA 161
Cdd:cd05343  167 VTA 169

human Mgc4172-like, classical (c) SDRs; Human Mgc4172-like proteins, putative SDRs. These proteins are members of the 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 228481714   1 GASGAIGGAIAIELVKSGMIVCALSRRRDKVEKLRVSLFDVA-GSLNYVECDITVEDDVKYAFGWIENTYGGVDMLVNNA 79
Cdd:cd05343   13 GASVGIGAAVARALVQHGMKVVGCARRVDKIEALAAECQSAGyPTLFPYQCDLSNEEQILSMFSAIRTQHQGVDVCINNA 92

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 228481714  80 GIITKCLLTEkNNTRDLYKTMETNIIGLSLCTREAVKSMKARDV-KGHIINVNSIFGHKVHQAvpgtrPLNGMYPASKYA 158
Cdd:cd05343   93 GLARPEPLLS-GKTEGWKEMFDVNVLALSICTREAYQSMKERNVdDGHIININSMSGHRVPPV-----SVFHFYAATKHA 166

                 ...
gi 228481714 159 VTA 161
Cdd:cd05343  167 VTA 169

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 228481714    1 GASGAIGGAIAIELVKSGMIVCALSRRRDKVEKLRVSLFDVAGSLNYVECDITVEDDVKYAFGWIENTYGGVDMLVNNAG 80
Cdd:pfam00106   7 GASSGIGRAIAKRLAKEGAKVVLVDRSEEKLEAVAKELGALGGKALFIQGDVTDRAQVKALVEQAVERLGRLDILVNNAG 86

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 228481714   81 IITKCLLTEKNNTrDLYKTMETNIIGLSLCTREAVKSMKARDvKGHIINVNSIFGHKvhqavpgTRPLNGMYPASKYAVT 160
Cdd:pfam00106  87 ITGLGPFSELSDE-DWERVIDVNLTGVFNLTRAVLPAMIKGS-GGRIVNISSVAGLV-------PYPGGSAYSASKAAVI 157

                  .
gi 228481714  161 A 161
Cdd:pfam00106 158 G 158

3-oxoacyl-(acyl-carrier-protein) reductase; This model represents 3-oxoacyl-[ACP] reductase, also called 3-ketoacyl-acyl carrier protein reductase, an enzyme of fatty acid biosynthesis. [Fatty acid and phospholipid metabolism, Biosynthesis]

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 228481714    1 GASGAIGGAIAIELVKSGMIVCALSRRRDK-VEKLRVSLFDVAGSLNYVECDITVEDDVKYAFGWIENTYGGVDMLVNNA 79
Cdd:TIGR01830   5 GASRGIGRAIALKLAKEGAKVIITYRSSEEgAEEVVEELKALGVKALGVVLDVSDREDVKAVVEEIEEELGTIDILVNNA 84

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 228481714   80 GIITKCLLTEKNNTrDLYKTMETNIIGLSLCTREAVKSM-KARdvKGHIINVNSIFG 135
Cdd:TIGR01830  85 GITRDNLLMRMKEE-DWDAVIDTNLTGVFNLTQAVLRIMiKQR--SGRIINISSVVG 138

human Mgc4172-like, classical (c) SDRs; Human Mgc4172-like proteins, putative SDRs. These proteins are members of the 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 228481714   1 GASGAIGGAIAIELVKSGMIVCALSRRRDKVEKLRVSLFDVA-GSLNYVECDITVEDDVKYAFGWIENTYGGVDMLVNNA 79
Cdd:cd05343   13 GASVGIGAAVARALVQHGMKVVGCARRVDKIEALAAECQSAGyPTLFPYQCDLSNEEQILSMFSAIRTQHQGVDVCINNA 92

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 228481714  80 GIITKCLLTEkNNTRDLYKTMETNIIGLSLCTREAVKSMKARDV-KGHIINVNSIFGHKVHQAvpgtrPLNGMYPASKYA 158
Cdd:cd05343   93 GLARPEPLLS-GKTEGWKEMFDVNVLALSICTREAYQSMKERNVdDGHIININSMSGHRVPPV-----SVFHFYAATKHA 166

                 ...
gi 228481714 159 VTA 161
Cdd:cd05343  167 VTA 169

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 228481714   1 GASGAIGGAIAIELVKSGMIVCALSRRRDKVEKLRVSLfdvAGSLNYVECDITVEDDVKYAFGWIENTYGGVDMLVNNAG 80
Cdd:COG4221   12 GASSGIGAATARALAAAGARVVLAARRAERLEALAAEL---GGRALAVPLDVTDEAAVEAAVAAAVAEFGRLDVLVNNAG 88

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 228481714  81 IITKCLLTEkNNTRDLYKTMETNIIGLSLCTREAVKSMKARDvKGHIINVNSIFGHKVhqavpgtRPLNGMYPASKYAVT 160
Cdd:COG4221   89 VALLGPLEE-LDPEDWDRMIDVNVKGVLYVTRAALPAMRARG-SGHIVNISSIAGLRP-------YPGGAVYAATKAAVR 159

                 .
gi 228481714 161 A 161
Cdd:COG4221  160 G 160

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 228481714    1 GASGAIGGAIAIELVKSGMIVCALSRRRDKVEKLRVSLFDVAGSLNYVECDITVEDDVKYAFGWIENTYGGVDMLVNNAG 80
Cdd:pfam00106   7 GASSGIGRAIAKRLAKEGAKVVLVDRSEEKLEAVAKELGALGGKALFIQGDVTDRAQVKALVEQAVERLGRLDILVNNAG 86

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 228481714   81 IITKCLLTEKNNTrDLYKTMETNIIGLSLCTREAVKSMKARDvKGHIINVNSIFGHKvhqavpgTRPLNGMYPASKYAVT 160
Cdd:pfam00106  87 ITGLGPFSELSDE-DWERVIDVNLTGVFNLTRAVLPAMIKGS-GGRIVNISSVAGLV-------PYPGGSAYSASKAAVI 157

                  .
gi 228481714  161 A 161
Cdd:pfam00106 158 G 158

glucose 1 dehydrogenase (GlcDH), classical (c) SDRs; GlcDH, is a tetrameric member of the SDR family, it catalyzes the NAD(P)-dependent oxidation of beta-D-glucose to D-glucono-delta-lactone. GlcDH has a typical NAD-binding site glycine-rich pattern as well as the canonical active site tetrad (YXXXK motif plus upstream Ser and Asn). 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 228481714   1 GASGAIGGAIAIELVKSGMIVCALSR-RRDKVEKLRVSLFDVAGSLNYVECDITVEDDVKYAFGWIENTYGGVDMLVNNA 79
Cdd:cd05358   10 GASSGIGKAIAIRLATAGANVVVNYRsKEDAAEEVVEEIKAVGGKAIAVQADVSKEEDVVALFQSAIKEFGTLDILVNNA 89

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 228481714  80 GIITKCLLTEKnNTRDLYKTMETNIIGLSLCTREAVKSMKARDVKGHIINVNSifghkVHQAVPgtRPLNGMYPASKYAV 159
Cdd:cd05358   90 GLQGDASSHEM-TLEDWNKVIDVNLTGQFLCAREAIKRFRKSKIKGKIINMSS-----VHEKIP--WPGHVNYAASKGGV 161

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 228481714   1 GASGAIGGAIAIELVKSGM-IVCALSRRRDKVEKLRVSLFDVAGSLNYVECDITVEDDVKYAFGWIENTYGGVDMLVNNA 79
Cdd:PRK05565  12 GASGGIGRAIAELLAKEGAkVVIAYDINEEAAQELLEEIKEEGGDAIAVKADVSSEEDVENLVEQIVEKFGKIDILVNNA 91

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 228481714  80 GIITKCLLTEKNNtRDLYKTMETNIIGLSLCTREAVKSMKARDvKGHIINVNSIFGhkvhqavpgtrpLNG-----MYPA 154
Cdd:PRK05565  92 GISNFGLVTDMTD-EEWDRVIDVNLTGVMLLTRYALPYMIKRK-SGVIVNISSIWG------------LIGascevLYSA 157

                 ....*..
gi 228481714 155 SKYAVTA 161
Cdd:PRK05565 158 SKGAVNA 164

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 228481714   1 GASGAIGGAIAIELVKSG--MIVCAlsRRRDKVEKLRVSLFDV-AGSLNYVECDITVEDDVKYAFGWIENTYGGVDMLVN 77
Cdd:cd05332   10 GASSGIGEELAYHLARLGarLVLSA--RREERLEEVKSECLELgAPSPHVVPLDMSDLEDAEQVVEEALKLFGGLDILIN 87

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 228481714  78 NAGIITKCLLTEknNTRDLYKT-METNIIGLSLCTREAVKSMKARDvKGHIINVNSIFGhKVhqAVPGTRPlngmYPASK 156
Cdd:cd05332   88 NAGISMRSLFHD--TSIDVDRKiMEVNYFGPVALTKAALPHLIERS-QGSIVVVSSIAG-KI--GVPFRTA----YAASK 157

                 ....*
gi 228481714 157 YAVTA 161
Cdd:cd05332  158 HALQG 162

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 228481714   1 GASGAIGGAIAIELVKSGMIVCALSRR-RDKVEKLRVSLFDVAGSLNYVECDITVEDDVKYAFGWIENTYGGVDMLVNNA 79
Cdd:PRK05557  12 GASRGIGRAIAERLAAQGANVVINYASsEAGAEALVAEIGALGGKALAVQGDVSDAESVERAVDEAKAEFGGVDILVNNA 91

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 228481714  80 GIITKCLLTEKNNtRDLYKTMETNIIGLSLCTREAVKSMKARDvKGHIINVNSIFGHK 137
Cdd:PRK05557  92 GITRDNLLMRMKE-EDWDRVIDTNLTGVFNLTKAVARPMMKQR-SGRIINISSVVGLM 147

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 228481714   1 GASGAIGGAIAIELVKSGMIVCALSRRRDKVEKLRVSLFDVAGslnyVECDITVEDDVKYAFGWIENTYGGVDMLVNNAG 80
Cdd:cd08932    7 GASRGIGIEIARALARDGYRVSLGLRNPEDLAALSASGGDVEA----VPYDARDPEDARALVDALRDRFGRIDVLVHNAG 82

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 228481714  81 IITKcLLTEKNNTRDLYKTMETNIIGLSLCTREAVKSMKARDvKGHIINVNSIFGHKVHQavpgtrpLNGMYPASKYAVT 160
Cdd:cd08932   83 IGRP-TTLREGSDAELEAHFSINVIAPAELTRALLPALREAG-SGRVVFLNSLSGKRVLA-------GNAGYSASKFALR 153

                 .
gi 228481714 161 A 161
Cdd:cd08932  154 A 154

SDR family oxidoreductase;

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 228481714   1 GASGAIGGAIAIELVKSGMIVCALSRRRDKVEKLR--VSLFDVAGSLNYVECDITVEDDVKyAFGWIENTYGGVDMLVNN 78
Cdd:PRK06914  10 GASSGFGLLTTLELAKKGYLVIATMRNPEKQENLLsqATQLNLQQNIKVQQLDVTDQNSIH-NFQLVLKEIGRIDLLVNN 88

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 228481714  79 AGIITKCLLtEKNNTRDLYKTMETNIIGLSLCTREAVKSMKARDvKGHIINVNSIFGhkvHQAVPGTRPlngmYPASKYA 158
Cdd:PRK06914  89 AGYANGGFV-EEIPVEEYRKQFETNVFGAISVTQAVLPYMRKQK-SGKIINISSISG---RVGFPGLSP----YVSSKYA 159

                 .
gi 228481714 159 V 159
Cdd:PRK06914 160 L 160

bifunctional aldolase/short-chain dehydrogenase;

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 228481714   1 GASGAIGGAIAIELVKSGMIVCALSRRRDKVEKLRVSLFDVAGSLNyVECDITVEDDVKYAFGWIENTYGGVDMLVNNAG 80
Cdd:PRK08324 429 GAAGGIGKATAKRLAAEGACVVLADLDEEAAEAAAAELGGPDRALG-VACDVTDEAAVQAAFEEAALAFGGVDIVVSNAG 507

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 228481714  81 I-ITKCLLTEknNTRDLYKTMETNIIGLSLCTREAVKSMKARDVKGHIINVNSifghkvHQAV-PGtrPLNGMYPASKYA 158
Cdd:PRK08324 508 IaISGPIEET--SDEDWRRSFDVNATGHFLVAREAVRIMKAQGLGGSIVFIAS------KNAVnPG--PNFGAYGAAKAA 577

SDR family oxidoreductase;

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 228481714   1 GASGAIGGAIAIELVKSGMIVCALSRRRDKVEKLrVSLFDVAGSLNYVECDITVEDDVKYAFGWIENTYGGVDMLVNNAG 80
Cdd:PRK07231  12 GASSGIGEGIARRFAAEGARVVVTDRNEEAAERV-AAEILAGGRAIAVAADVSDEADVEAAVAAALERFGSVDILVNNAG 90

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 228481714  81 I--ITKCLLTEKNNTRDlyKTMETNIIGLSLCTREAVKSMKARDvKGHIINVNSIFGHKvhqavpgTRPLNGMYPASKYA 158
Cdd:PRK07231  91 TthRNGPLLDVDEAEFD--RIFAVNVKSPYLWTQAAVPAMRGEG-GGAIVNVASTAGLR-------PRPGLGWYNASKGA 160

                 .
gi 228481714 159 V 159
Cdd:PRK07231 161 V 161

3-hydroxybutyrate dehydrogenase; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 228481714   1 GASGAIGGAIAIELVKSGMIVCALSRRRDKVEKLRVSLFDVAGSLNYVECDITVEDDVKYAFGWIENTYGGVDMLVNNAG 80
Cdd:PRK12429  11 GAASGIGLEIALALAKEGAKVVIADLNDEAAAAAAEALQKAGGKAIGVAMDVTDEEAINAGIDYAVETFGGVDILVNNAG 90

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 228481714  81 IITKCLLtEKNNTRDLYKTMETNIIGLSLCTREAVKSMKARDVkGHIINVNSIFGH 136
Cdd:PRK12429  91 IQHVAPI-EDFPTEKWKKMIAIMLDGAFLTTKAALPIMKAQGG-GRIINMASVHGL 144

human 17-beta-hydroxysteroid dehydrogenase XI-like, classical (c) SDRs; 17-beta-hydroxysteroid dehydrogenases (17betaHSD) are a group of isozymes that catalyze activation and inactivation of estrogen and androgens. 17betaHSD type XI, a classical SDR, preferentially converts 3alpha-Adiol to androsterone but not numerous other tested steroids. This subgroup of classical SDRs also includes members identified as retinol dehydrogenases, which convert retinol to retinal, a property that overlaps with 17betaHSD activity. 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 228481714   1 GASGAIGGAIAIELVKSGMIVCALSRRRDKVEKLRVSLFDVAGSLNYVECDITVEDDVKYAFGWIENTYGGVDMLVNNAG 80
Cdd:cd05339    6 GGGSGIGRLLALEFAKRGAKVVILDINEKGAEETANNVRKAGGKVHYYKCDVSKREEVYEAAKKIKKEVGDVTILINNAG 85

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 228481714  81 IITKCLLTEKNNtRDLYKTMETNIIGLSLCTREAVKSMKARDvKGHIINVNSIFGHKvhqavpgtrPLNGM--YPASKYA 158
Cdd:cd05339   86 VVSGKKLLELPD-EEIEKTFEVNTLAHFWTTKAFLPDMLERN-HGHIVTIASVAGLI---------SPAGLadYCASKAA 154

                 ...
gi 228481714 159 VTA 161
Cdd:cd05339  155 AVG 157

Enoyl-(Acyl carrier protein) reductase; This domain is found in Enoyl-(Acyl carrier protein) reductases.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 228481714    6 IGGAIAIELVKSG--MIVCALSRR-RDKVEKLRVSLFDVAgslnyVECDITVEDDVKYAFGWIENTYGGVDMLVNNAGII 82
Cdd:pfam13561   8 IGWAIARALAEEGaeVVLTDLNEAlAKRVEELAEELGAAV-----LPCDVTDEEQVEALVAAAVEKFGRLDILVNNAGFA 82

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 228481714   83 TKCLLTEKNNTRDLY-KTMETNIIGLSLCTREAVKSMKARdvkGHIINVNSIFGHKVhqaVPGtrplNGMYPASKYAV 159
Cdd:pfam13561  83 PKLKGPFLDTSREDFdRALDVNLYSLFLLAKAALPLMKEG---GSIVNLSSIGAERV---VPN----YNAYGAAKAAL 150

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 228481714   1 GASGAIGGAIAIELVKSGMIVCALSRRRDK----VEKLRVSLFDVAGSLNYVECDITVEDDVKYAFGWIENTYGGVDMLV 76
Cdd:cd08939    8 GGSSGIGKALAKELVKEGANVIIVARSESKleeaVEEIEAEANASGQKVSYISADLSDYEEVEQAFAQAVEKGGPPDLVV 87

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 228481714  77 NNAGIITkCLLTEKNNTRDLYKTMETNIIGLSLCTREAVKSMKARDvKGHIINVNSifghkvhQAvpGTRPLNG--MYPA 154
Cdd:cd08939   88 NCAGISI-PGLFEDLTAEEFERGMDVNYFGSLNVAHAVLPLMKEQR-PGHIVFVSS-------QA--ALVGIYGysAYCP 156

                 ....*
gi 228481714 155 SKYAV 159
Cdd:cd08939  157 SKFAL 161

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 228481714   1 GASGAIGGAIAIELVKSGMIVCALSRRRDKVEKLRVSLFDVAGSLNYVECDITVEDDVKYAFGWIENTYGGVDMLVNNAG 80
Cdd:cd05350    5 GASSGIGRALAREFAKAGYNVALAARRTDRLDELKAELLNPNPSVEVEILDVTDEERNQLVIAELEAELGGLDLVIINAG 84

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 228481714  81 I--ITKCLLTEKNNTRdlyKTMETNIIGLSLCTREAVKSMKARDvKGHIINVNSIFGHKvhqAVPGTrplnGMYPASKYA 158
Cdd:cd05350   85 VgkGTSLGDLSFKAFR---ETIDTNLLGAAAILEAALPQFRAKG-RGHLVLISSVAALR---GLPGA----AAYSASKAA 153

                 ...
gi 228481714 159 VTA 161
Cdd:cd05350  154 LSS 156

rhamnulose-1-phosphate aldolase/alcohol dehydrogenase, classical (c) SDRs; This family has bifunctional proteins with an N-terminal aldolase and a C-terminal classical SDR domain. One member is identified as a rhamnulose-1-phosphate aldolase/alcohol dehydrogenase. The SDR domain has a canonical SDR glycine-rich NAD(P) binding motif and a match to the characteristic active site triad. However, it lacks an upstream active site Asn typical of 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 228481714   1 GASGAIGGAIAIELVKSGMIVCALSRRRDKVEKLRVSLFDVAGSLNyVECDITVEDDVKYAFGWIENTYGGVDMLVNNAG 80
Cdd:cd08943    8 GGASGIGLAIAKRLAAEGAAVVVADIDPEIAEKVAEAAQGGPRALG-VQCDVTSEAQVQSAFEQAVLEFGGLDIVVSNAG 86