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< | ==Crystal structure of an alpha-L-fucosidase GH29 trapped covalent intermediate from Bacteroides thetaiotaomicron in complex with 2- fluoro-fucosyl fluoride using an E288Q mutant== | ||
<StructureSection load='2wvs' size='340' side='right'caption='[[2wvs]], [[Resolution|resolution]] 2.19Å' scene=''> | |||
You may | == Structural highlights == | ||
<table><tr><td colspan='2'>[[2wvs]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Bacteroides_thetaiotaomicron_VPI-5482 Bacteroides thetaiotaomicron VPI-5482]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2WVS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2WVS FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.19Å</td></tr> | |||
- | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FUF:2-DEOXY-2-FLUORO-BETA-L-FUCOPYRANOSE'>FUF</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></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=2wvs FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2wvs OCA], [https://pdbe.org/2wvs PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2wvs RCSB], [https://www.ebi.ac.uk/pdbsum/2wvs PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2wvs ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/Q8A3I4_BACTN Q8A3I4_BACTN] | |||
== Evolutionary Conservation == | |||
[[Image:Consurf_key_small.gif|200px|right]] | |||
Check<jmol> | |||
<jmolCheckbox> | |||
<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/wv/2wvs_consurf.spt"</scriptWhenChecked> | |||
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked> | |||
<text>to colour the structure by Evolutionary Conservation</text> | |||
</jmolCheckbox> | |||
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2wvs ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The enzymatic hydrolysis of alpha-l-fucosides is of importance in cancer, bacterial infections, and fucosidosis, a neurodegenerative lysosomal storage disorder. Here we show a series of snapshots along the reaction coordinate of a glycoside hydrolase family GH29 alpha-l-fucosidase unveiling a Michaelis (ES) complex in a (1)C(4) (chair) conformation and a covalent glycosyl-enzyme intermediate in (3)S(1) (skew-boat). First principles metadynamics simulations on isolated alpha-l-fucose strongly support a (1)C(4)<-->(3)H(4)<-->(3)S(1) conformational itinerary for the glycosylation step of the reaction mechanism and indicate a strong "preactivation" of the (1)C(4) complex to nucleophilic attack as reflected by free energy, C1-O1/O5-C1 bond length elongation/reduction, C1-O1 bond orientation, and positive charge development around the anomeric carbon. Analysis of an imino sugar inhibitor is consistent with tight binding of a chair-conformed charged species. | |||
Analysis of the Reaction Coordinate of alpha-l-Fucosidases: A Combined Structural and Quantum Mechanical Approach.,Lammerts van Bueren A, Fayers-Kerr J, Luo B, Zhang Y, Sollogoub M, Bleriot Y, Rovira C, Davies GJ J Am Chem Soc. 2010 Jan 21. PMID:20092273<ref>PMID:20092273</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 2wvs" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
== | [[Category: Bacteroides thetaiotaomicron VPI-5482]] | ||
[[Category: Large Structures]] | |||
[[Category: Ardevol A]] | |||
== | [[Category: Bleriot Y]] | ||
< | [[Category: Davies GJ]] | ||
[[Category: Bacteroides thetaiotaomicron]] | [[Category: Fayers-Kerr J]] | ||
[[Category: Ardevol | [[Category: Lammerts van Bueren A]] | ||
[[Category: Bleriot | [[Category: Luo B]] | ||
[[Category: | [[Category: Rovira C]] | ||
[[Category: | [[Category: Sollogoub M]] | ||
[[Category: | [[Category: Zhang Y]] | ||
[[Category: Luo | |||
[[Category: Rovira | |||
[[Category: Sollogoub | |||
[[Category: Zhang | |||
Latest revision as of 12:35, 6 November 2024
Crystal structure of an alpha-L-fucosidase GH29 trapped covalent intermediate from Bacteroides thetaiotaomicron in complex with 2- fluoro-fucosyl fluoride using an E288Q mutantCrystal structure of an alpha-L-fucosidase GH29 trapped covalent intermediate from Bacteroides thetaiotaomicron in complex with 2- fluoro-fucosyl fluoride using an E288Q mutant
Structural highlights
FunctionEvolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedThe enzymatic hydrolysis of alpha-l-fucosides is of importance in cancer, bacterial infections, and fucosidosis, a neurodegenerative lysosomal storage disorder. Here we show a series of snapshots along the reaction coordinate of a glycoside hydrolase family GH29 alpha-l-fucosidase unveiling a Michaelis (ES) complex in a (1)C(4) (chair) conformation and a covalent glycosyl-enzyme intermediate in (3)S(1) (skew-boat). First principles metadynamics simulations on isolated alpha-l-fucose strongly support a (1)C(4)<-->(3)H(4)<-->(3)S(1) conformational itinerary for the glycosylation step of the reaction mechanism and indicate a strong "preactivation" of the (1)C(4) complex to nucleophilic attack as reflected by free energy, C1-O1/O5-C1 bond length elongation/reduction, C1-O1 bond orientation, and positive charge development around the anomeric carbon. Analysis of an imino sugar inhibitor is consistent with tight binding of a chair-conformed charged species. Analysis of the Reaction Coordinate of alpha-l-Fucosidases: A Combined Structural and Quantum Mechanical Approach.,Lammerts van Bueren A, Fayers-Kerr J, Luo B, Zhang Y, Sollogoub M, Bleriot Y, Rovira C, Davies GJ J Am Chem Soc. 2010 Jan 21. PMID:20092273[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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