GDP-mannose 4,6-dehydratase; Alternate name: GDP-D-mannose dehydratase. This enzyme converts GDP-mannose to GDP-4-dehydro-6-deoxy-D-mannose, the first of three steps for the conversion of GDP-mannose to GDP-fucose in animals, plants, and bacteria. In bacteria, GDP-L-fucose acts as a precursor of surface antigens such as the extracellular polysaccharide colanic acid of E. coli. Excluded from this model are members of the clade that score poorly because of highly dervied (phylogenetically long-branch) sequences, e.g. Aneurinibacillus thermoaerophilus Gmd, described as a bifunctional GDP-mannose 4,6-dehydratase/GDP-6-deoxy-D-lyxo-4-hexulose reductase (PUBMED:11096116). [Cell envelope, Biosynthesis and degradation of surface polysaccharides and lipopolysaccharides]

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767939783   24 NVALITGITGQDGSYLAEFLLEKGYEVHGIVRRSSSFNTGRIEHLYKNPQAHIEGNMKLHYGDLTDSTCLVKIINEVKPT 103
Cdd:TIGR01472   1 KIALITGITGQDGSYLAEFLLEKGYEVHGLIRRSSSFNTQRIEHIYEDPHNVNKARMKLHYGDLTDSSNLRRIIDEIKPT 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767939783  104 EIYNLGAQSHVKISFDLAEYTADVDGVGTLRLLDAVKTCGLINSVKFYQASTSELYGKVQEIPQKETTPFYPRSPYGAAK 183
Cdd:TIGR01472  81 EIYNLAAQSHVKVSFEIPEYTADVDGIGTLRLLEAVRTLGLIKSVKFYQASTSELYGKVQEIPQNETTPFYPRSPYAAAK 160

                         170       180       190
                  ....*....|....*....|....*....|..
gi 767939783  184 LYAYWIVVNFREAYNLFAVNGILFNHESPRRG 215
Cdd:TIGR01472 161 LYAHWITVNYREAYGLFAVNGILFNHESPRRG 192

GDP-mannose 4,6 dehydratase, extended (e) SDRs; GDP-mannose 4,6 dehydratase, a homodimeric SDR, catalyzes the NADP(H)-dependent conversion of GDP-(D)-mannose to GDP-4-keto, 6-deoxy-(D)-mannose in the fucose biosynthesis pathway. These proteins have the canonical active site triad and NAD-binding pattern, however the active site Asn is often missing and may be substituted with Asp. A Glu residue has been identified as an important active site base. Extended SDRs are distinct from classical SDRs. In addition to the Rossmann fold (alpha/beta folding pattern with a central beta-sheet) core region typical of all SDRs, extended SDRs have a less conserved C-terminal extension of approximately 100 amino acids. Extended SDRs are a diverse collection of proteins, and include isomerases, epimerases, oxidoreductases, and lyases; they typically have a TGXXGXXG cofactor binding motif. SDRs are a functionally diverse family of oxidoreductases that have a single domain with a structurally conserved Rossmann fold, an NAD(P)(H)-binding region, and a structurally diverse C-terminal region. Sequence identity between different SDR enzymes is typically in the 15-30% range; they 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 numbering). In addition to the Tyr and Lys, there is often an upstream Ser and/or an Asn, 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. Atypical SDRs generally lack the catalytic residues characteristic of the SDRs, and their glycine-rich NAD(P)-binding motif is often different from the forms normally seen in classical or extended SDRs. 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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767939783  25 VALITGITGQDGSYLAEFLLEKGYEVHGIVRRSSSFNTGRIEHLYknpqaHIEGNMKLHYGDLTDSTCLVKIINEVKPTE 104
Cdd:cd05260    1 RALITGITGQDGSYLAEFLLEKGYEVHGIVRRSSSFNTDRIDHLY-----INKDRITLHYGDLTDSSSLRRAIEKVRPDE 75

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767939783 105 IYNLGAQSHVKISFDLAEYTADVDGVGTLRLLDAVKTCGLinSVKFYQASTSELYGKVQEIPQKETTPFYPRSPYGAAKL 184
Cdd:cd05260   76 IYHLAAQSHVKVSFDDPEYTAEVNAVGTLNLLEAIRILGL--DARFYQASSSEEYGKVQELPQSETTPFRPRSPYAVSKL 153

                        170       180       190
                 ....*....|....*....|....*....|.
gi 767939783 185 YAYWIVVNFREAYNLFAVNGILFNHESPRRG 215
Cdd:cd05260  154 YADWITRNYREAYGLFAVNGRLFNHEGPRRG 184

GDP-mannose 4,6-dehydratase; Alternate name: GDP-D-mannose dehydratase. This enzyme converts GDP-mannose to GDP-4-dehydro-6-deoxy-D-mannose, the first of three steps for the conversion of GDP-mannose to GDP-fucose in animals, plants, and bacteria. In bacteria, GDP-L-fucose acts as a precursor of surface antigens such as the extracellular polysaccharide colanic acid of E. coli. Excluded from this model are members of the clade that score poorly because of highly dervied (phylogenetically long-branch) sequences, e.g. Aneurinibacillus thermoaerophilus Gmd, described as a bifunctional GDP-mannose 4,6-dehydratase/GDP-6-deoxy-D-lyxo-4-hexulose reductase (PUBMED:11096116). [Cell envelope, Biosynthesis and degradation of surface polysaccharides and lipopolysaccharides]

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767939783   24 NVALITGITGQDGSYLAEFLLEKGYEVHGIVRRSSSFNTGRIEHLYKNPQAHIEGNMKLHYGDLTDSTCLVKIINEVKPT 103
Cdd:TIGR01472   1 KIALITGITGQDGSYLAEFLLEKGYEVHGLIRRSSSFNTQRIEHIYEDPHNVNKARMKLHYGDLTDSSNLRRIIDEIKPT 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767939783  104 EIYNLGAQSHVKISFDLAEYTADVDGVGTLRLLDAVKTCGLINSVKFYQASTSELYGKVQEIPQKETTPFYPRSPYGAAK 183
Cdd:TIGR01472  81 EIYNLAAQSHVKVSFEIPEYTADVDGIGTLRLLEAVRTLGLIKSVKFYQASTSELYGKVQEIPQNETTPFYPRSPYAAAK 160

                         170       180       190
                  ....*....|....*....|....*....|..
gi 767939783  184 LYAYWIVVNFREAYNLFAVNGILFNHESPRRG 215
Cdd:TIGR01472 161 LYAHWITVNYREAYGLFAVNGILFNHESPRRG 192

GDP-mannose 4,6 dehydratase, extended (e) SDRs; GDP-mannose 4,6 dehydratase, a homodimeric SDR, catalyzes the NADP(H)-dependent conversion of GDP-(D)-mannose to GDP-4-keto, 6-deoxy-(D)-mannose in the fucose biosynthesis pathway. These proteins have the canonical active site triad and NAD-binding pattern, however the active site Asn is often missing and may be substituted with Asp. A Glu residue has been identified as an important active site base. Extended SDRs are distinct from classical SDRs. In addition to the Rossmann fold (alpha/beta folding pattern with a central beta-sheet) core region typical of all SDRs, extended SDRs have a less conserved C-terminal extension of approximately 100 amino acids. Extended SDRs are a diverse collection of proteins, and include isomerases, epimerases, oxidoreductases, and lyases; they typically have a TGXXGXXG cofactor binding motif. SDRs are a functionally diverse family of oxidoreductases that have a single domain with a structurally conserved Rossmann fold, an NAD(P)(H)-binding region, and a structurally diverse C-terminal region. Sequence identity between different SDR enzymes is typically in the 15-30% range; they 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 numbering). In addition to the Tyr and Lys, there is often an upstream Ser and/or an Asn, 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. Atypical SDRs generally lack the catalytic residues characteristic of the SDRs, and their glycine-rich NAD(P)-binding motif is often different from the forms normally seen in classical or extended SDRs. 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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767939783  25 VALITGITGQDGSYLAEFLLEKGYEVHGIVRRSSSFNTGRIEHLYknpqaHIEGNMKLHYGDLTDSTCLVKIINEVKPTE 104
Cdd:cd05260    1 RALITGITGQDGSYLAEFLLEKGYEVHGIVRRSSSFNTDRIDHLY-----INKDRITLHYGDLTDSSSLRRAIEKVRPDE 75

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767939783 105 IYNLGAQSHVKISFDLAEYTADVDGVGTLRLLDAVKTCGLinSVKFYQASTSELYGKVQEIPQKETTPFYPRSPYGAAKL 184
Cdd:cd05260   76 IYHLAAQSHVKVSFDDPEYTAEVNAVGTLNLLEAIRILGL--DARFYQASSSEEYGKVQELPQSETTPFRPRSPYAVSKL 153

                        170       180       190
                 ....*....|....*....|....*....|.
gi 767939783 185 YAYWIVVNFREAYNLFAVNGILFNHESPRRG 215
Cdd:cd05260  154 YADWITRNYREAYGLFAVNGRLFNHEGPRRG 184

NAD dependent epimerase/dehydratase family; This family of proteins utilize NAD as a cofactor. The proteins in this family use nucleotide-sugar substrates for a variety of chemical reactions.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767939783   26 ALITGITGQDGSYLAEFLLEKGYEVHGIVRRSSSFNTGRIEHLyknpqahiegnmKLHYGDLTDSTCLVKIINEVKPTEI 105
Cdd:pfam01370   1 ILVTGATGFIGSHLVRRLLEKGYEVIGLDRLTSASNTARLADL------------RFVEGDLTDRDALEKLLADVRPDAV 68

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767939783  106 YNLGAQSHVKISFDLAEYTADVDGVGTLRLLDAVKTCGLinsVKFYQASTSELYGKVQEIPQKETT---PFYPRSPYGAA 182
Cdd:pfam01370  69 IHLAAVGGVGASIEDPEDFIEANVLGTLNLLEAARKAGV---KRFLFASSSEVYGDGAEIPQEETTltgPLAPNSPYAAA 145

                         170       180       190
                  ....*....|....*....|....*....|...
gi 767939783  183 KLYAYWIVVNFREAYNLFAVNGILFNHESPRRG 215
Cdd:pfam01370 146 KLAGEWLVLAYAAAYGLRAVILRLFNVYGPGDN 178

Nucleoside-diphosphate-sugar epimerase [Cell wall/membrane/envelope biogenesis];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767939783  27 LITGITGQDGSYLAEFLLEKGYEVHGIVRRSSSFntGRIEHLyknpqahieGNMKLHYGDLTDSTCLVKIINevKPTEIY 106
Cdd:COG0451    3 LVTGGAGFIGSHLARRLLARGHEVVGLDRSPPGA--ANLAAL---------PGVEFVRGDLRDPEALAAALA--GVDAVV 69

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767939783 107 NLGAQSHVKIsfDLAEYTADVDGVGTLRLLDAVKTCGLInsvKFYQASTSELYGKvQEIPQKETTPFYPRSPYGAAKLYA 186
Cdd:COG0451   70 HLAAPAGVGE--EDPDETLEVNVEGTLNLLEAARAAGVK---RFVYASSSSVYGD-GEGPIDEDTPLRPVSPYGASKLAA 143

                        170
                 ....*....|....*.
gi 767939783 187 YWIVVNFREAYNLFAV 202
Cdd:COG0451  144 ELLARAYARRYGLPVT 159

UDP-glucuronate decarboxylase (UGD) and related proteins, extended (e) SDRs; UGD catalyzes the formation of UDP-xylose from UDP-glucuronate; it is an extended-SDR, and has the characteristic glycine-rich NAD-binding pattern, TGXXGXXG, and active site tetrad. Extended SDRs are distinct from classical SDRs. In addition to the Rossmann fold (alpha/beta folding pattern with a central beta-sheet) core region typical of all SDRs, extended SDRs have a less conserved C-terminal extension of approximately 100 amino acids. Extended SDRs are a diverse collection of proteins, and include isomerases, epimerases, oxidoreductases, and lyases; they typically have a TGXXGXXG cofactor binding motif. SDRs are a functionally diverse family of oxidoreductases that have a single domain with a structurally conserved Rossmann fold, an NAD(P)(H)-binding region, and a structurally diverse C-terminal region. Sequence identity between different SDR enzymes is typically in the 15-30% range; they 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 numbering). In addition to the Tyr and Lys, there is often an upstream Ser and/or an Asn, 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. Atypical SDRs generally lack the catalytic residues characteristic of the SDRs, and their glycine-rich NAD(P)-binding motif is often different from the forms normally seen in classical or extended SDRs. 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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767939783  26 ALITGITGQDGSYLAEFLLEKGYEVHGIvrrsSSFNTGR---IEHLYKNPqahiegNMKLHYGDLTDSTclvkiinEVKP 102
Cdd:cd05230    3 ILITGGAGFLGSHLCDRLLEDGHEVICV----DNFFTGRkrnIEHLIGHP------NFEFIRHDVTEPL-------YLEV 65

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767939783 103 TEIYNLGAQ-SHVKISFDLAEyTADVDGVGTLRLLDAVKTCGlinsVKFYQASTSELYGKVQEIPQKET-----TPFYPR 176
Cdd:cd05230   66 DQIYHLACPaSPVHYQYNPIK-TLKTNVLGTLNMLGLAKRVG----ARVLLASTSEVYGDPEVHPQPESywgnvNPIGPR 140

                        170       180
                 ....*....|....*....|...
gi 767939783 177 SPYGAAKLYAYWIVVNFREAYNL 199
Cdd:cd05230  141 SCYDEGKRVAETLCMAYHRQHGV 163

UDP-glucose 4 epimerase, subgroup 1, extended (e) SDRs; UDP-glucose 4 epimerase (aka UDP-galactose-4-epimerase), is a homodimeric extended SDR. It catalyzes the NAD-dependent conversion of UDP-galactose to UDP-glucose, the final step in Leloir galactose synthesis. This subgroup has the characteristic active site tetrad and NAD-binding motif of the extended SDRs. Extended SDRs are distinct from classical SDRs. In addition to the Rossmann fold (alpha/beta folding pattern with a central beta-sheet) core region typical of all SDRs, extended SDRs have a less conserved C-terminal extension of approximately 100 amino acids. Extended SDRs are a diverse collection of proteins, and include isomerases, epimerases, oxidoreductases, and lyases; they typically have a TGXXGXXG cofactor binding motif. SDRs are a functionally diverse family of oxidoreductases that have a single domain with a structurally conserved Rossmann fold, an NAD(P)(H)-binding region, and a structurally diverse C-terminal region. Sequence identity between different SDR enzymes is typically in the 15-30% range; they 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 numbering). In addition to the Tyr and Lys, there is often an upstream Ser and/or an Asn, 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. Atypical SDRs generally lack the catalytic residues characteristic of the SDRs, and their glycine-rich NAD(P)-binding motif is often different from the forms normally seen in classical or extended SDRs. 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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767939783  27 LITGITGQDGSYLAEFLLEKGYEVHGIvrrsSSFNTGRIEHLYKNPQAHIEgnmkLHYGDLTDSTCLVKIINEVKPTEIY 106
Cdd:cd05247    3 LVTGGAGYIGSHTVVELLEAGYDVVVL----DNLSNGHREALPRIEKIRIE----FYEGDIRDRAALDKVFAEHKIDAVI 74

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767939783 107 NLGAQSHVKIS--FDLAEYTADVdgVGTLRLLDAVKTCGLINSVkFyqASTSELYGKVQEIPQKETTPFYPRSPYGAAKL 184
Cdd:cd05247   75 HFAALKAVGESvqKPLKYYDNNV--VGTLNLLEAMRAHGVKNFV-F--SSSAAVYGEPETVPITEEAPLNPTNPYGRTKL 149

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....
gi 767939783 185 YAYWIVVNFREAYNLFAVngIL--FN----HESPRRG-----------YVVDVA 221
Cdd:cd05247  150 MVEQILRDLAKAPGLNYV--ILryFNpagaHPSGLIGedpqipnnlipYVLQVA 201

UDP glucuronic acid epimerase, extended (e) SDRs; This subgroup contains UDP-D-glucuronic acid 4-epimerase, an extended SDR, which catalyzes the conversion of UDP-alpha-D-glucuronic acid to UDP-alpha-D-galacturonic acid. This group has the SDR's canonical catalytic tetrad and the TGxxGxxG NAD-binding motif of the extended SDRs. Extended SDRs are distinct from classical SDRs. In addition to the Rossmann fold (alpha/beta folding pattern with a central beta-sheet) core region typical of all SDRs, extended SDRs have a less conserved C-terminal extension of approximately 100 amino acids. Extended SDRs are a diverse collection of proteins, and include isomerases, epimerases, oxidoreductases, and lyases; they typically have a TGXXGXXG cofactor binding motif. SDRs are a functionally diverse family of oxidoreductases that have a single domain with a structurally conserved Rossmann fold, an NAD(P)(H)-binding region, and a structurally diverse C-terminal region. Sequence identity between different SDR enzymes is typically in the 15-30% range; they 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 numbering). In addition to the Tyr and Lys, there is often an upstream Ser and/or an Asn, 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. Atypical SDRs generally lack the catalytic residues characteristic of the SDRs, and their glycine-rich NAD(P)-binding motif is often different from the forms normally seen in classical or extended SDRs. 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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767939783  27 LITGITGQDGSYLAEFLLEKGYEVHGIVRRSSSFNT----GRIEHLYKnpqahiEGNMKLHYGDLTDSTCLVKIINEVKP 102
Cdd:cd05253    4 LVTGAAGFIGFHVAKRLLERGDEVVGIDNLNDYYDVrlkeARLELLGK------SGGFKFVKGDLEDREALRRLFKDHEF 77

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767939783 103 TEIYNLGAQSHVKISFDLAEYTADVDGVGTLRLLDAvktCGLINSVKFYQASTSELYGKVQEIPQKETTPF-YPRSPYGA 181
Cdd:cd05253   78 DAVIHLAAQAGVRYSLENPHAYVDSNIVGFLNLLEL---CRHFGVKHLVYASSSSVYGLNTKMPFSEDDRVdHPISLYAA 154

                 ..
gi 767939783 182 AK 183
Cdd:cd05253  155 TK 156

Arna decarboxylase_like, extended (e) SDRs; Decarboxylase domain of ArnA. ArnA, is an enzyme involved in the modification of outer membrane protein lipid A of gram-negative bacteria. It is a bifunctional enzyme that catalyzes the NAD-dependent decarboxylation of UDP-glucuronic acid and N-10-formyltetrahydrofolate-dependent formylation of UDP-4-amino-4-deoxy-l-arabinose; its NAD-dependent decaboxylating activity is in the C-terminal 360 residues. This subgroup belongs to the extended SDR family, however the NAD binding motif is not a perfect match and the upstream Asn of the canonical active site tetrad is not conserved. Extended SDRs are distinct from classical SDRs. In addition to the Rossmann fold (alpha/beta folding pattern with a central beta-sheet) core region typical of all SDRs, extended SDRs have a less conserved C-terminal extension of approximately 100 amino acids. Extended SDRs are a diverse collection of proteins, and include isomerases, epimerases, oxidoreductases, and lyases; they typically have a TGXXGXXG cofactor binding motif. SDRs are a functionally diverse family of oxidoreductases that have a single domain with a structurally conserved Rossmann fold, an NAD(P)(H)-binding region, and a structurally diverse C-terminal region. Sequence identity between different SDR enzymes is typically in the 15-30% range; they 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 numbering). In addition to the Tyr and Lys, there is often an upstream Ser and/or an Asn, 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. Atypical SDRs generally lack the catalytic residues characteristic of the SDRs, and their glycine-rich NAD(P)-binding motif is often different from the forms normally seen in classical or extended SDRs. 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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767939783  27 LITGITGQDGSYLAEFLLEKGYEVHGIVRRSSsfntgRIEHLYKNPQAHIEgnMKLHYGDLTDStclVKIINEVKPTE-I 105
Cdd:cd05257    3 LVTGADGFIGSHLTERLLREGHEVRALDIYNS-----FNSWGLLDNAVHDR--FHFISGDVRDA---SEVEYLVKKCDvV 72

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767939783 106 YNLGAqsHVKISFdlaEYTADVDGV-----GTLRLLDAVktCGLINSvKFYQASTSELYGKVQEIPQKETTPFY----PR 176
Cdd:cd05257   73 FHLAA--LIAIPY---SYTAPLSYVetnvfGTLNVLEAA--CVLYRK-RVVHTSTSEVYGTAQDVPIDEDHPLLyinkPR 144

                        170
                 ....*....|
gi 767939783 177 SPYGAAKLYA 186
Cdd:cd05257  145 SPYSASKQGA 154

dTDP-glucose 4,6-dehydratase

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767939783   5 PARCPSARGSGDGEMGK-PRNVA------LITGITGQDGSYLAEFLLEKGYEVHGIvrrsSSFNTGRIE---HLYKNPQa 74
Cdd:PLN02166  95 PSSSTFNSSGGGGRTGRvPVGIGrkrlriVVTGGAGFVGSHLVDKLIGRGDEVIVI----DNFFTGRKEnlvHLFGNPR- 169

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767939783  75 hiegnMKLHYGDLTDStclvkIINEVKptEIYNLGA-QSHVKISFDLAEyTADVDGVGTLRLLDAVKTCGlinsVKFYQA 153
Cdd:PLN02166 170 -----FELIRHDVVEP-----ILLEVD--QIYHLACpASPVHYKYNPVK-TIKTNVMGTLNMLGLAKRVG----ARFLLT 232

                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 767939783 154 STSELYGKVQEIPQKET-----TPFYPRSPYGAAKLYAYWIVVNFREAYNLFAVNGILFNHESPR 213
Cdd:PLN02166 233 STSEVYGDPLEHPQKETywgnvNPIGERSCYDEGKRTAETLAMDYHRGAGVEVRIARIFNTYGPR 297

Bordetella bronchiseptica enzymes WbmH and WbmG-like, extended (e) SDRs; Bordetella bronchiseptica enzymes WbmH and WbmG, and related proteins. This subgroup exhibits the active site tetrad and NAD-binding motif of the extended SDR family. It has been proposed that the active site in Bordetella WbmG and WbmH cannot function as an epimerase, and that it plays a role in O-antigen synthesis pathway from UDP-2,3-diacetamido-2,3-dideoxy-l-galacturonic acid. Extended SDRs are distinct from classical SDRs. In addition to the Rossmann fold (alpha/beta folding pattern with a central beta-sheet) core region typical of all SDRs, extended SDRs have a less conserved C-terminal extension of approximately 100 amino acids. Extended SDRs are a diverse collection of proteins, and include isomerases, epimerases, oxidoreductases, and lyases; they typically have a TGXXGXXG cofactor binding motif. SDRs are a functionally diverse family of oxidoreductases that have a single domain with a structurally conserved Rossmann fold, an NAD(P)(H)-binding region, and a structurally diverse C-terminal region. Sequence identity between different SDR enzymes is typically in the 15-30% range; they 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 numbering). In addition to the Tyr and Lys, there is often an upstream Ser and/or an Asn, 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. Atypical SDRs generally lack the catalytic residues characteristic of the SDRs, and their glycine-rich NAD(P)-binding motif is often different from the forms normally seen in classical or extended SDRs. 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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767939783  27 LITGITGQDGSYLAEFLLEKGYEVHGIvrrsSSFNTGRIEHLYKNPqahiegNMKLHYGDLTDSTCLVKIINEVKPTEIY 106
Cdd:cd08957    4 LITGGAGQIGSHLIEHLLERGHQVVVI----DNFATGRREHLPDHP------NLTVVEGSIADKALVDKLFGDFKPDAVV 73

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 767939783 107 NLGAQshVKISFDLAEYTAdVDGVGTLRLLDAVKTCGLINSVKFyqaSTSELYG-KVQEIPQKETTP-FYPRSPYGAAK 183
Cdd:cd08957   74 HTAAA--YKDPDDWYEDTL-TNVVGGANVVQAAKKAGVKRLIYF---QTALCYGlKPMQQPIRLDHPrAPPGSSYAISK 146

dTDP-4-dehydrorhamnose reductase [Cell wall/membrane/envelope biogenesis];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767939783  27 LITGITGQDGSYLAEFLLEKGYEVHGIVRRSssfntgriehlyknpqahiegnmklhyGDLTDSTCLVKIINEVKPTEIY 106
Cdd:COG1091    3 LVTGANGQLGRALVRLLAERGYEVVALDRSE---------------------------LDITDPEAVAALLEEVRPDVVI 55

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767939783 107 NLGAQSHVkisfDLAE------YTADVDGVGTLrlldaVKTCGLINsVKFYQASTSelY---GKvQEIPQKETTPFYPRS 177
Cdd:COG1091   56 NAAAYTAV----DKAEsepelaYAVNATGPANL-----AEACAELG-ARLIHISTD--YvfdGT-KGTPYTEDDPPNPLN 122

                 ....*..
gi 767939783 178 PYGAAKL 184
Cdd:COG1091  123 VYGRSKL 129

dTDP-6-deoxy-L-lyxo-4-hexulose reductase and related proteins, extended (e) SDRs; dTDP-6-deoxy-L-lyxo-4-hexulose reductase, an extended SDR, synthesizes dTDP-L-rhamnose from alpha-D-glucose-1-phosphate, providing the precursor of L-rhamnose, an essential cell wall component of many pathogenic bacteria. This subgroup has the characteristic active site tetrad and NADP-binding motif. This subgroup also contains human MAT2B, the regulatory subunit of methionine adenosyltransferase (MAT); MAT catalyzes S-adenosylmethionine synthesis. The human gene encoding MAT2B encodes two major splicing variants which are induced in human cell liver cancer and regulate HuR, an mRNA-binding protein which stabilizes the mRNA of several cyclins, to affect cell proliferation. Both MAT2B variants include this extended SDR domain. Extended SDRs are distinct from classical SDRs. In addition to the Rossmann fold (alpha/beta folding pattern with a central beta-sheet) core region typical of all SDRs, extended SDRs have a less conserved C-terminal extension of approximately 100 amino acids. Extended SDRs are a diverse collection of proteins, and include isomerases, epimerases, oxidoreductases, and lyases; they typically have a TGXXGXXG cofactor binding motif. SDRs are a functionally diverse family of oxidoreductases that have a single domain with a structurally conserved Rossmann fold, an NAD(P)(H)-binding region, and a structurally diverse C-terminal region. Sequence identity between different SDR enzymes is typically in the 15-30% range; they 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 numbering). In addition to the Tyr and Lys, there is often an upstream Ser and/or an Asn, 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. Atypical SDRs generally lack the catalytic residues characteristic of the SDRs, and their glycine-rich NAD(P)-binding motif is often different from the forms normally seen in classical or extended SDRs. 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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767939783  27 LITGITGQDGSYLAEFLLEKGYEVHGIVRRSSSFntgriehlyknpqahiegnmklHYGDLTDSTCLVKIINEVKPTEIY 106
Cdd:cd05254    3 LITGATGMLGRALVRLLKERGYEVIGTGRSRASL----------------------FKLDLTDPDAVEEAIRDYKPDVII 60

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767939783 107 NLGAQSHVkisfDLAE------YTADVDGVGTLrlldaVKTCGLINSvKFYQASTSELY-GKvqEIPQKETTPFYPRSPY 179
Cdd:cd05254   61 NCAAYTRV----DKCEsdpelaYRVNVLAPENL-----ARAAKEVGA-RLIHISTDYVFdGK--KGPYKEEDAPNPLNVY 128

                 ....*
gi 767939783 180 GAAKL 184
Cdd:cd05254  129 GKSKL 133

probable rhamnose biosynthetic enzyme

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767939783  17 GEMGKPRNVaLITGITGQDGSYLAEFLLeKGYEVHGIVRRSSSFNTGRIEHLykNPQAHIEgNMKLHYGDLTDStclvKI 96
Cdd:PLN02260   1 MATYEPKNI-LITGAAGFIASHVANRLI-RNYPDYKIVVLDKLDYCSNLKNL--NPSKSSP-NFKFVKGDIASA----DL 71

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767939783  97 INEVKPTE----IYNLGAQSHVKISF-DLAEYTADvDGVGTLRLLDAVKTCGLINsvKFYQASTSELYGKVQE---IPQK 168
Cdd:PLN02260  72 VNYLLITEgidtIMHFAAQTHVDNSFgNSFEFTKN-NIYGTHVLLEACKVTGQIR--RFIHVSTDEVYGETDEdadVGNH 148

                        170       180       190
                 ....*....|....*....|....*....|.
gi 767939783 169 ETTPFYPRSPYGAAKLYAYWIVVNFREAYNL 199
Cdd:PLN02260 149 EASQLLPTNPYSATKAGAEMLVMAYGRSYGL 179

RmlD substrate binding domain; L-rhamnose is a saccharide required for the virulence of some bacteria. Its precursor, dTDP-L-rhamnose, is synthesized by four different enzymes the final one of which is RmlD. The RmlD substrate binding domain is responsible for binding a sugar nucleotide.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767939783   27 LITGITGQDGSYLAEFLLEKGYEVHGIVRRSssfntgriehlyknpqahiegnmklhyGDLTDSTCLVKIINEVKPTEIY 106
Cdd:pfam04321   2 LITGANGQLGTELRRLLAERGIEVVALTRAE---------------------------LDLTDPEAVARLLREIKPDVVV 54

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767939783  107 NLGAQSHVkisfDLAE------YTADVDGVGTLrlldaVKTCGLINsVKFYQASTSELYGKVQEIPQKETTPFYPRSPYG 180
Cdd:pfam04321  55 NAAAYTAV----DKAEsepdlaYAINALAPANL-----AEACAAVG-APLIHISTDYVFDGTKPRPYEEDDETNPLNVYG 124

                  ....
gi 767939783  181 AAKL 184
Cdd:pfam04321 125 RTKL 128

UDP-galactose-4-epimerase; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767939783  27 LITGITGQDGSYLAEFLLEKGYEVHGI--VRRSSSFNTGRIEHLYKNPQAHIEGnmklhygDLTDSTCLVKIINEVKPTE 104
Cdd:PRK10675   4 LVTGGSGYIGSHTCVQLLQNGHDVVILdnLCNSKRSVLPVIERLGGKHPTFVEG-------DIRNEALLTEILHDHAIDT 76

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767939783 105 IYNLGAQSHV--KISFDLAEYTADVDGvgTLRLLDAVKTCGLINsvkFYQASTSELYGKVQEIPQKETTPF-YPRSPYGA 181
Cdd:PRK10675  77 VIHFAGLKAVgeSVQKPLEYYDNNVNG--TLRLISAMRAANVKN---LIFSSSATVYGDQPKIPYVESFPTgTPQSPYGK 151

                        170
                 ....*....|....*
gi 767939783 182 AKLYAYWIVVNFREA 196
Cdd:PRK10675 152 SKLMVEQILTDLQKA 166

UDP-glucose 4-epimerase (G4E), subgroup 5, extended (e) SDRs; This subgroup partially conserves the characteristic active site tetrad and NAD-binding motif of the extended SDRs, and has been identified as possible UDP-glucose 4-epimerase (aka UDP-galactose 4-epimerase), a homodimeric member of the extended SDR family. UDP-glucose 4-epimerase catalyzes the NAD-dependent conversion of UDP-galactose to UDP-glucose, the final step in Leloir galactose synthesis. Extended SDRs are distinct from classical SDRs. In addition to the Rossmann fold (alpha/beta folding pattern with a central beta-sheet) core region typical of all SDRs, extended SDRs have a less conserved C-terminal extension of approximately 100 amino acids. Extended SDRs are a diverse collection of proteins, and include isomerases, epimerases, oxidoreductases, and lyases; they typically have a TGXXGXXG cofactor binding motif. SDRs are a functionally diverse family of oxidoreductases that have a single domain with a structurally conserved Rossmann fold, an NAD(P)(H)-binding region, and a structurally diverse C-terminal region. Sequence identity between different SDR enzymes is typically in the 15-30% range; they 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 numbering). In addition to the Tyr and Lys, there is often an upstream Ser and/or an Asn, 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. Atypical SDRs generally lack the catalytic residues characteristic of the SDRs, and their glycine-rich NAD(P)-binding motif is often different from the forms normally seen in classical or extended SDRs. 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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767939783  26 ALITGITGQDGSYLAEFLLEKGYEVHGIVRRSS--SFNTGRIEhlyknpqahiegnmkLHYGDLTDSTCLVKIINEVKpT 103
Cdd:cd05264    2 VLIVGGNGFIGSHLVDALLEEGPQVRVFDRSIPpyELPLGGVD---------------YIKGDYENRADLESALVGID-T 65

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767939783 104 EIY----NLGAQSHVKISFDLAEytadvDGVGTLRLLDAvktCGLINSVKFYQASTS-ELYGKVQEIPQKETTPFYPRSP 178
Cdd:cd05264   66 VIHlastTNPATSNKNPILDIQT-----NVAPTVQLLEA---CAAAGIGKIIFASSGgTVYGVPEQLPISESDPTLPISS 137

                        170       180
                 ....*....|....*....|.
gi 767939783 179 YGAAKLYAYWIVVNFREAYNL 199
Cdd:cd05264  138 YGISKLAIEKYLRLYQYLYGL 158

human NSDHL (NAD(P)H steroid dehydrogenase-like protein)-like, extended (e) SDRs; This subgroup includes human NSDHL and related proteins. These proteins have the characteristic active site tetrad of extended SDRs, and also have a close match to their NAD(P)-binding motif. Human NSDHL is a 3beta-hydroxysteroid dehydrogenase (3 beta-HSD) which functions in the cholesterol biosynthetic pathway. 3 beta-HSD catalyzes the oxidative conversion of delta 5-3 beta-hydroxysteroids to the delta 4-3-keto configuration; this activity is essential for the biosynthesis of all classes of hormonal steroids. Mutations in the gene encoding NSDHL cause CHILD syndrome (congenital hemidysplasia with ichthyosiform nevus and limb defects), an X-linked dominant, male-lethal trait. This subgroup also includes an unusual bifunctional [3beta-hydroxysteroid dehydrogenase (3b-HSD)/C-4 decarboxylase from Arabidopsis thaliana, and Saccharomyces cerevisiae ERG26, a 3b-HSD/C-4 decarboxylase, involved in the synthesis of ergosterol, the major sterol of yeast. Extended SDRs are distinct from classical SDRs. In addition to the Rossmann fold (alpha/beta folding pattern with a central beta-sheet) core region typical of all SDRs, extended SDRs have a less conserved C-terminal extension of approximately 100 amino acids. Extended SDRs are a diverse collection of proteins, and include isomerases, epimerases, oxidoreductases, and lyases; they typically have a TGXXGXXG cofactor binding motif. SDRs are a functionally diverse family of oxidoreductases that have a single domain with a structurally conserved Rossmann fold, an NAD(P)(H)-binding region, and a structurally diverse C-terminal region. Sequence identity between different SDR enzymes is typically in the 15-30% range; they 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 numbering). In addition to the Tyr and Lys, there is often an upstream Ser and/or an Asn, 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. Atypical SDRs generally lack the catalytic residues characteristic of the SDRs, and their glycine-rich NAD(P)-binding motif is often different from the forms normally seen in classical or extended SDRs. Complex (multidomain) SDRs such as ketoreductase domains of fatty acid sythase 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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767939783  27 LITGITGQDGSYLAEFLLEKG-YEVHgivrrssSFNTGRIEHLykNPQAHieGNMKLHYGDLTDSTCLVKIINEVKPTEI 105
Cdd:cd09813    3 LVVGGSGFLGRHLVEQLLRRGnPTVH-------VFDIRPTFEL--DPSSS--GRVQFHTGDLTDPQDLEKAFNEKGPNVV 71