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 1720410129   1 MRAHGVKNLVFSSSATVYGNPQYLPLDEAHPTGgCTNPYGKSKFFIEEMIRDLCRADTaWNAVLLRYFNPIGAHASGRIG 80
Cdd:cd05247   107 MRAHGVKNFVFSSSAAVYGEPETVPITEEAPLN-PTNPYGRTKLMVEQILRDLAKAPG-LNYVILRYFNPAGAHPSGLIG 184

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720410129  81 EDPQgIPNNLMPYVSQVAIGRREALNVFGDDYATEDGTGVRDYIHVVDLAKGHIAALKKLKEQCGCRTYNLGTGTGYSVL 160
Cdd:cd05247   185 EDPQ-IPNNLIPYVLQVALGRREKLAIFGDDYPTPDGTCVRDYIHVVDLADAHVLALEKLENGGGSEIYNLGTGRGYSVL 263

                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720410129 161 QMVQAMEKASGKKIPYKVVARREGDVAACYANPSLAHEELGWTAALGLDRMCEDLWRWQK 220
Cdd:cd05247   264 EVVEAFEKVSGKPIPYEIAPRRAGDPASLVADPSKAREELGWKPKRDLEDMCEDAWNWQS 323

UDP-glucose-4-epimerase GalE; Alternate name: UDPgalactose 4-epimerase This enzyme interconverts UDP-glucose and UDP-galactose. A set of related proteins, some of which are tentatively identified as UDP-glucose-4-epimerase in Thermotoga maritima, Bacillus halodurans, and several archaea, but deeply branched from this set and lacking experimental evidence, are excluded from this model and described by a separate model. [Energy metabolism, Sugars]

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720410129   1 MRAHGVKNLVFSSSATVYGNPQYLPLDEAHPTGGcTNPYGKSKFFIEEMIRDLCRADTAWNAVLLRYFNPIGAHASGRIG 80
Cdd:TIGR01179 108 MQQAGVKKFIFSSSAAVYGEPSSIPISEDSPLGP-INPYGRSKLMSEQILRDLQKADPDWSYVILRYFNVAGAHPSGDIG 186

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720410129  81 EDPQGIPNnLMPYVSQVAIGRREALNVFGDDYATEDGTGVRDYIHVVDLAKGHIAALKKLKEQCGCRTYNLGTGTGYSVL 160
Cdd:TIGR01179 187 EDPPGITH-LIPYACQVAVGKRDKLTIFGTDYPTPDGTCVRDYIHVMDLADAHLAALEYLLNGGGSHVYNLGYGQGFSVL 265

                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1720410129 161 QMVQAMEKASGKKIPYKVVARREGDVAACYANPSLAHEELGWTAALG-LDRMCEDLWRWQKQN 222
Cdd:TIGR01179 266 EVIEAFKKVSGKDFPVELAPRRPGDPASLVADASKIRRELGWQPKYTdLEEIIKDAWRWESRN 328

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 1720410129   1 MRAHGVKNLVFSSSATVYGNPQYLPLDEAHPTGgCTNPYGKSKFFIEEMIRDLCRADTaWNAVLLRYFNPIGAHASGRIG 80
Cdd:cd05247   107 MRAHGVKNFVFSSSAAVYGEPETVPITEEAPLN-PTNPYGRTKLMVEQILRDLAKAPG-LNYVILRYFNPAGAHPSGLIG 184

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720410129  81 EDPQgIPNNLMPYVSQVAIGRREALNVFGDDYATEDGTGVRDYIHVVDLAKGHIAALKKLKEQCGCRTYNLGTGTGYSVL 160
Cdd:cd05247   185 EDPQ-IPNNLIPYVLQVALGRREKLAIFGDDYPTPDGTCVRDYIHVVDLADAHVLALEKLENGGGSEIYNLGTGRGYSVL 263

                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720410129 161 QMVQAMEKASGKKIPYKVVARREGDVAACYANPSLAHEELGWTAALGLDRMCEDLWRWQK 220
Cdd:cd05247   264 EVVEAFEKVSGKPIPYEIAPRRAGDPASLVADPSKAREELGWKPKRDLEDMCEDAWNWQS 323

UDP-galactose-4-epimerase; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720410129   1 MRAHGVKNLVFSSSATVYGNPQYLPLDEAHPTGGCTNPYGKSKFFIEEMIRDLCRADTAWNAVLLRYFNPIGAHASGRIG 80
Cdd:PRK10675  111 MRAANVKNLIFSSSATVYGDQPKIPYVESFPTGTPQSPYGKSKLMVEQILTDLQKAQPDWSIALLRYFNPVGAHPSGDMG 190

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720410129  81 EDPQGIPNNLMPYVSQVAIGRREALNVFGDDYATEDGTGVRDYIHVVDLAKGHIAALKKLKEQCGCRTYNLGTGTGYSVL 160
Cdd:PRK10675  191 EDPQGIPNNLMPYIAQVAVGRRDSLAIFGNDYPTEDGTGVRDYIHVMDLADGHVAAMEKLANKPGVHIYNLGAGVGSSVL 270

                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1720410129 161 QMVQAMEKASGKKIPYKVVARREGDVAACYANPSLAHEELGWTAALGLDRMCEDLWRWQKQNPSGF 226
Cdd:PRK10675  271 DVVNAFSKACGKPVNYHFAPRREGDLPAYWADASKADRELNWRVTRTLDEMAQDTWHWQSRHPQGY 336

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720410129   1 MRAHGVKNLVFSSSATVYGNPQyLPLDEAHPTGGcTNPYGKSKFFIEEMIRDLCRADtAWNAVLLRYFNPIGAHASGRIg 80
Cdd:COG0451   100 ARAAGVKRFVYASSSSVYGDGE-GPIDEDTPLRP-VSPYGASKLAAELLARAYARRY-GLPVTILRPGNVYGPGDRGVL- 175

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720410129  81 edpqgipNNLMPyvsqvAIGRREALNVFGddyateDGTGVRDYIHVVDLAKGHIAALKklKEQCGCRTYNLGTGTGYSVL 160
Cdd:COG0451   176 -------PRLIR-----RALAGEPVPVFG------DGDQRRDFIHVDDVARAIVLALE--APAAPGGVYNVGGGEPVTLR 235

                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1720410129 161 QMVQAMEKASGKKIPYkVVARREGDVAACYANPSLAHEELGWTAALGLDRMCEDLWRWQKQ 221
Cdd:COG0451   236 ELAEAIAEALGRPPEI-VYPARPGDVRPRRADNSKARRELGWRPRTSLEEGLRETVAWYRA 295

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 1720410129   1 MRAHGVKNLVF-SSSATVYGNPQYLPLDEAHPTGGcTNPYGKSKFFIEEMIRdLCRADTAWNAVLLRYFNPIGAhasgri 79
Cdd:cd05264   100 CAAAGIGKIIFaSSGGTVYGVPEQLPISESDPTLP-ISSYGISKLAIEKYLR-LYQYLYGLDYTVLRISNPYGP------ 171

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720410129  80 GEDPQGIpnnlmpyvsQVAIG-------RREALNVFGDdyatedGTGVRDYIHVVDLAKGHIAALKKLKEqcgCRTYNLG 152
Cdd:cd05264   172 GQRPDGK---------QGVIPialnkilRGEPIEIWGD------GESIRDYIYIDDLVEALMALLRSKGL---EEVFNIG 233

                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1720410129 153 TGTGYSVLQMVQAMEKASGKKIPYKVVARREGDVAACYANPSLAHEELGWTAALGLDRMCEDLWRW 218
Cdd:cd05264   234 SGIGYSLAELIAEIEKVTGRSVQVIYTPARTTDVPKIVLDISRARAELGWSPKISLEDGLEKTWQW 299

extended (e) 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 1720410129   1 MRAHGVKNLVFSSSATVYGNPQYLPLDEAHPTgGCTNPYGKSKFFIEEMIRDLCRADTaWNAVLLRYFNPIGAHASGRig 80
Cdd:cd08946    68 ARKAGVKRFVYASSASVYGSPEGLPEEEETPP-RPLSPYGVSKLAAEHLLRSYGESYG-LPVVILRLANVYGPGQRPR-- 143

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1720410129  81 edpqgiPNNLMPYVSQVAIGRREaLNVFGddyateDGTGVRDYIHVVDLAKGHIAALKklKEQCGCRTYNLG 152
Cdd:cd08946   144 ------LDGVVNDFIRRALEGKP-LTVFG------GGNQTRDFIHVDDVVRAILHALE--NPLEGGGVYNIG 200

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 1720410129   5 GVKNLVFSSSATVYGNPQYLPLDEAHPTGGCTN---PYGKSKFFIEEMIRDLCRADTAwNAVLLRYFNPIGAHASGRige 81
Cdd:cd05257   110 YRKRVVHTSTSEVYGTAQDVPIDEDHPLLYINKprsPYSASKQGADRLAYSYGRSFGL-PVTIIRPFNTYGPRQSAR--- 185

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720410129  82 dpQGIPNnlmpYVSQVAIGRREALNVfgddyateDGTGVRDYIHVVDLAKGHIAALkkLKEQCGCRTYNLGTGTGYSV-- 159
Cdd:cd05257   186 --AVIPT----IISQRAIGQRLINLG--------DGSPTRDFNFVKDTARGFIDIL--DAIEAVGEIINNGSGEEISIgn 249

                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1720410129 160 -LQMVQAMEKASGKKIPYKVVAR-REG--DVAACYANPSLAHEELGWTAALGLDRMCEDLWRWQKQN 222
Cdd:cd05257   250 pAVELIVEELGEMVLIVYDDHREyRPGysEVERRIPDIRKAKRLLGWEPKYSLRDGLRETIEWFKDQ 316

dTDP-D-glucose 4,6-dehydratase [Cell wall/membrane/envelope biogenesis];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720410129   2 RAHGV--KNLVFSSSATVYGN-PQYLPLDEAHPTGGcTNPYGKSKFFIEEMIRdlcradtAW------NAVLLRYFNPIG 72
Cdd:COG1088   114 RKYWVegFRFHHVSTDEVYGSlGEDGPFTETTPLDP-SSPYSASKAASDHLVR-------AYhrtyglPVVITRCSNNYG 185

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720410129  73 AHASgrigedpqgiPNNLMPYVSQVAI-GRReaLNVFGDdyatedGTGVRDYIHVVDLAKGHIAALKKLKeqCGcRTYNL 151
Cdd:COG1088   186 PYQF----------PEKLIPLFITNALeGKP--LPVYGD------GKQVRDWLYVEDHCRAIDLVLEKGR--PG-ETYNI 244

                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1720410129 152 GTGTGYSVLQMVQAMEKASGK-KIPYKVVARREGDVaACYA-NPSLAHEELGWTAALGLDRMCEDLWRWQKQNPS 224
Cdd:COG1088   245 GGGNELSNLEVVELICDLLGKpESLITFVKDRPGHD-RRYAiDASKIRRELGWKPKVTFEEGLRKTVDWYLDNRD 318

CDP-tyvelose 2-epimerase, extended (e) SDRs; CDP-tyvelose 2-epimerase is a tetrameric SDR that catalyzes the conversion of CDP-D-paratose to CDP-D-tyvelose, the last step in tyvelose biosynthesis. This subgroup is a member of the extended SDR subfamily, with a characteristic active site tetrad and NAD-binding motif. 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 1720410129   1 MRAHGVK-NLVFSSSATVYGN-PQYLPL-------------------DEAHPTGGCTNPYGKSKFFIEEMIRDLCRAdTA 59
Cdd:cd05258   111 ARQHAPNaPFIFTSTNKVYGDlPNYLPLeeletryelapegwspagiSESFPLDFSHSLYGASKGAADQYVQEYGRI-FG 189

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720410129  60 WNAVLLRYFNPIGAHASGRigEDpQGIPNNLMpyvsQVAIgRREALNVFGDDyatedGTGVRDYIHVVDLAKGHIAALKK 139
Cdd:cd05258   190 LKTVVFRCGCLTGPRQFGT--ED-QGWVAYFL----KCAV-TGKPLTIFGYG-----GKQVRDVLHSADLVNLYLRQFQN 256

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720410129 140 LKEQCGcRTYNLGTGTGYSV--LQMVQAMEKASGKKIPYKVVARREGDVAACYANPSLAHEELGWTAALGLDRMCEDLWR 217
Cdd:cd05258   257 PDRRKG-EVFNIGGGRENSVslLELIALCEEITGRKMESYKDENRPGDQIWYISDIRKIKEKPGWKPERDPREILAEIYA 335

                  ..
gi 1720410129 218 WQ 219
Cdd:cd05258   336 WI 337

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 1720410129   1 MRAHGVK-NLVFSSSATVYGNPQYLPLDEAHPTGGcTNPYGKSKFFIEEMIRdLCRADTAWNAVLLRYFNpigaHASGRI 79
Cdd:cd05260   110 IRILGLDaRFYQASSSEEYGKVQELPQSETTPFRP-RSPYAVSKLYADWITR-NYREAYGLFAVNGRLFN----HEGPRR 183

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720410129  80 GED--PQGIpnnlmpyVSQVA---IGRREAL---NVfgddyatedgTGVRDYIHVVDLAKGHIAALKKLKEQcgcrTYNL 151
Cdd:cd05260   184 GETfvTRKI-------TRQVArikAGLQPVLklgNL----------DAKRDWGDARDYVEAYWLLLQQGEPD----DYVI 242

                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1720410129 152 GTGTGYSVLQMV-QAMEKASGKKIPYKVV--AR-REGDVAACYANPSLAHEELGWTAALGLdrmcEDLWRWQ 219
Cdd:cd05260   243 ATGETHSVREFVeLAFEESGLTGDIEVEIdpRYfRPTEVDLLLGDPSKAREELGWKPEVSF----EELVREM 310

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 1720410129   2 RAHGVKNLVFSSSATVYGNP---QYLPLDeaHPTGGCTNPYGKSKFFIEE--MIRDLcradtawNAVLLRYFNPIGahas 76
Cdd:cd08957   104 KKAGVKRLIYFQTALCYGLKpmqQPIRLD--HPRAPPGSSYAISKTAGEYylELSGV-------DFVTFRLANVTG---- 170

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720410129  77 grigedPQGIPNNLMPYVSQVAIGRrealNVFGDDyatedgtGVRDYIHVVDLAKghiAALKKLKEQCGCRTYNLGTGTG 156
Cdd:cd08957   171 ------PRNVIGPLPTFYQRLKAGK----KCFVTD-------TRRDFVFVKDLAR---VVDKALDGIRGHGAYHFSSGED 230

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1720410129 157 YSVLQM----VQAMEKASGKKIPykVVARREGDVAACYANPSLAHEELGWTAALGL 208
Cdd:cd08957   231 VSIKELfdavVEALDLPLRPEVE--VVELGPDDVPSILLDPSRTFQDFGWKEFTPL 284

UDP-glucose 4 epimerase (G4E), subgroup 3, extended (e) SDRs; Members of this bacterial subgroup are identified as possible sugar epimerases, such as UDP-glucose 4 epimerase. However, while the NAD(P)-binding motif is fairly well conserved, not all members retain the canonical active site tetrad of the extended 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. 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 1720410129   1 MRAHGVKNLVFSSSATVYG----NPqyLPLDEAHPTGGCTN-PYGKSKFFIEEMIRDLCRADTAWNAVLLRYFNPIGAHA 75
Cdd:cd05240    97 CAAAGVPRVVVTSSVAVYGahpdNP--APLTEDAPLRGSPEfAYSRDKAEVEQLLAEFRRRHPELNVTVLRPATILGPGT 174

Vi polysaccharide biosynthesis UDP-N-acetylglucosaminuronic acid C-4 epimerase TviC;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720410129   3 AHgVKNLVFSSSATVYGNPQYLPLDEAHpTGGCTNPYGKSKFfIEEMIRDLCRADTAWNAVLLRYFNPIGAHasgrigED 82
Cdd:PRK15181  131 AH-VSSFTYAASSSTYGDHPDLPKIEER-IGRPLSPYAVTKY-VNELYADVFARSYEFNAIGLRYFNVFGRR------QN 201

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720410129  83 PQGIPNNLMPyvsqvaigrREALNVFGDD--YATEDGTGVRDYIHVVDLAKGHIAALKKLKEQCGCRTYNLGTGTGYSVL 160
Cdd:PRK15181  202 PNGAYSAVIP---------RWILSLLKDEpiYINGDGSTSRDFCYIENVIQANLLSATTNDLASKNKVYNVAVGDRTSLN 272

                  ..
gi 1720410129 161 QM 162
Cdd:PRK15181  273 EL 274

UDP-glucose 4 epimerase, subgroup 4, 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 is comprised of bacterial proteins, and includes the Staphylococcus aureus capsular polysaccharide Cap5N, which may have a role in the synthesis of UDP-N-acetyl-d-fucosamine. 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 1720410129   3 AHGVKNLVFSSSATVYGNP-QYLPLDEAHPTGGcTNPYGKSKFFIEEMIRDLCrADTAWNAVLLRYfnPI--GAHASGRI 79
Cdd:cd05232    99 RQGVKRFVFLSSVKVNGEGtVGAPFDETDPPAP-QDAYGRSKLEAERALLELG-ASDGMEVVILRP--PMvyGPGVRGNF 174

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720410129  80 GEDPQ----GIPnnLMPYVSQvaiGRREALNVFgddyatedgtgvrdyiHVVDLAkGHIAALKKLKEQcgcrTYNLGTGT 155
Cdd:cd05232   175 ARLMRlidrGLP--LPPGAVK---NRRSLVSLD----------------NLVDAI-YLCISLPKAANG----TFLVSDGP 228

                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1720410129 156 GYSVLQMVQAMEKASGKK--------IPYKVVARREGDVAACYA-------NPSLAHEELGWTAALGLD 209
Cdd:cd05232   229 PVSTAELVDEIRRALGKPtrllpvpaGLLRFAAKLLGKRAVIQRlfgslqyDPEKTQNELGWRPPISLE 297