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| | ==Crystal Structure Analysis of WbgU: a UDP-GalNAc 4-epimerase== | | ==Crystal Structure Analysis of WbgU: a UDP-GalNAc 4-epimerase== |
| - | <StructureSection load='3lu1' size='340' side='right' caption='[[3lu1]], [[Resolution|resolution]] 2.50Å' scene=''> | + | <StructureSection load='3lu1' size='340' side='right'caption='[[3lu1]], [[Resolution|resolution]] 2.50Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3lu1]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/"aeromonas_shigelloides"_(bader_1954)_ewing_et_al._1961 "aeromonas shigelloides" (bader 1954) ewing et al. 1961]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3LU1 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3LU1 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3lu1]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Plesiomonas_shigelloides Plesiomonas shigelloides]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3LU1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3LU1 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GLY:GLYCINE'>GLY</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=NAD:NICOTINAMIDE-ADENINE-DINUCLEOTIDE'>NAD</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=UD2:URIDINE-DIPHOSPHATE-N-ACETYLGALACTOSAMINE'>UD2</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.5Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">wbgU ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=703 "Aeromonas shigelloides" (Bader 1954) Ewing et al. 1961])</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GLY:GLYCINE'>GLY</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=NAD:NICOTINAMIDE-ADENINE-DINUCLEOTIDE'>NAD</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=UD2:URIDINE-DIPHOSPHATE-N-ACETYLGALACTOSAMINE'>UD2</scene></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Isomerase Isomerase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=5.1.3.7 5.1.3.7] </span></td></tr>
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3lu1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3lu1 OCA], [https://pdbe.org/3lu1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3lu1 RCSB], [https://www.ebi.ac.uk/pdbsum/3lu1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3lu1 ProSAT]</span></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3lu1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3lu1 OCA], [http://pdbe.org/3lu1 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3lu1 RCSB], [http://www.ebi.ac.uk/pdbsum/3lu1 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3lu1 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/GNE_PLESH GNE_PLESH] Catalyzes the epimerization of UDP-N-acetylglucosamine (UDP-GlcNAc) to UDP-N-acetylgalactosamine (UDP-GalNAc). Has very low epimerase activity with UDP-Glc and UDP-Gal. Plays a role in the biosynthesis of 2-acetamino-2-deoxy-L-altruronic acid, a building block of the O-antigen in bacterial lipopolysaccharide (LPS).<ref>PMID:12484781</ref> <ref>PMID:21810411</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
| | Check<jmol> | | Check<jmol> |
| | <jmolCheckbox> | | <jmolCheckbox> |
| - | <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/lu/3lu1_consurf.spt"</scriptWhenChecked> | + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/lu/3lu1_consurf.spt"</scriptWhenChecked> |
| | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> |
| | <text>to colour the structure by Evolutionary Conservation</text> | | <text>to colour the structure by Evolutionary Conservation</text> |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Isomerase]] | + | [[Category: Large Structures]] |
| - | [[Category: Bhatt, V S]] | + | [[Category: Plesiomonas shigelloides]] |
| - | [[Category: Guo, C Y]] | + | [[Category: Bhatt VS]] |
| - | [[Category: Liu, Z J]] | + | [[Category: Guo CY]] |
| - | [[Category: Wang, P G]] | + | [[Category: Liu ZJ]] |
| - | [[Category: Yi, W]] | + | [[Category: Wang PG]] |
| - | [[Category: Zhao, G]] | + | [[Category: Yi W]] |
| - | [[Category: Epimerase]]
| + | [[Category: Zhao G]] |
| - | [[Category: Glycan]]
| + | |
| - | [[Category: Lipopolysaccharide]]
| + | |
| - | [[Category: Nadh]]
| + | |
| - | [[Category: Rossmann fold]]
| + | |
| - | [[Category: Udp-glcnac]]
| + | |
| Structural highlights
3lu1 is a 4 chain structure with sequence from Plesiomonas shigelloides. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Method: | X-ray diffraction, Resolution 2.5Å |
| Ligands: | , , , , |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
GNE_PLESH Catalyzes the epimerization of UDP-N-acetylglucosamine (UDP-GlcNAc) to UDP-N-acetylgalactosamine (UDP-GalNAc). Has very low epimerase activity with UDP-Glc and UDP-Gal. Plays a role in the biosynthesis of 2-acetamino-2-deoxy-L-altruronic acid, a building block of the O-antigen in bacterial lipopolysaccharide (LPS).[1] [2]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
UDP-hexose 4-epimerases play a pivotal role in lipopolysaccharide (LPS) biosynthesis and Leloir pathway. These epimerases are classified into three groups based on whether they recognize nonacetylated UDP-hexoses (Group 1), both N-acetylated and nonacetylated UDP-hexoses (Group 2) or only N-acetylated UDP-hexoses (Group 3). Although the catalysis has been investigated extensively, yet a definitive model rationalizing the substrate specificity of all the three groups on a common platform is largely lacking. In this work, we present the crystal structure of WbgU, a novel UDP-hexose 4-epimerase that belongs to the Group 3. WbgU is involved in biosynthetic pathway of the unusual glycan 2-deoxy-L-altruronic acid that is found in the LPS of the pathogen Pleisomonas shigelloides. A model that defines its substrate specificity is proposed on the basis of the active site architecture. Representatives from all the three groups are then compared to rationalize their substrate specificity. This investigation reveals that the Group 3 active site architecture is markedly different from the "conserved scaffold" of the Group 1 and the Group 2 epimerases and highlights the interactions potentially responsible for the origin of specificity of the Group 3 epimerases toward N-acetylated hexoses. This study provides a platform for further engineering of the UDP-hexose 4-epimerases, leads to a deeper understanding of the LPS biosynthesis and carbohydrate recognition by proteins. It may also have implications in development of novel antibiotics and more economic synthesis of UDP-GalNAc and downstream products such as carbohydrate based vaccines.
Altered architecture of substrate binding region defines the unique specificity of UDP-GalNAc 4-epimerases.,Bhatt VS, Guo CY, Guan W, Zhao G, Yi W, Liu ZJ, Wang PG Protein Sci. 2011 May;20(5):856-66. doi: 10.1002/pro.611. Epub 2011 Apr 5. PMID:21384454[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Kowal P, Wang PG. New UDP-GlcNAc C4 epimerase involved in the biosynthesis of 2-acetamino-2-deoxy-L-altruronic acid in the O-antigen repeating units of Plesiomonas shigelloides O17. Biochemistry. 2002 Dec 24;41(51):15410-4. PMID:12484781 doi:10.1021/bi026384i
- ↑ Bhatt VS, Guan W, Xue M, Yuan H, Wang PG. Insights into role of the hydrogen bond networks in substrate recognition by UDP-GalNAc 4-epimerases. Biochem Biophys Res Commun. 2011 Aug 26;412(2):232-7. PMID:21810411 doi:10.1016/j.bbrc.2011.07.071
- ↑ Bhatt VS, Guo CY, Guan W, Zhao G, Yi W, Liu ZJ, Wang PG. Altered architecture of substrate binding region defines the unique specificity of UDP-GalNAc 4-epimerases. Protein Sci. 2011 May;20(5):856-66. doi: 10.1002/pro.611. Epub 2011 Apr 5. PMID:21384454 doi:10.1002/pro.611
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