View source for 2wvt


==Crystal structure of an alpha-L-fucosidase GH29 from Bacteroides thetaiotaomicron in complex with a novel iminosugar fucosidase inhibitor==
<StructureSection load='2wvt' size='340' side='right'caption='[[2wvt]], [[Resolution|resolution]] 1.80&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2wvt]] is a 2 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=2WVT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2WVT 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]] 1.8&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FHN:(2S,3R,5R,6S)-3,4,5-TRIHYDROXY-2,6-BIS(HYDROXYMETHYL)PIPERIDINIUM'>FHN</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=IMD:IMIDAZOLE'>IMD</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=2wvt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2wvt OCA], [https://pdbe.org/2wvt PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2wvt RCSB], [https://www.ebi.ac.uk/pdbsum/2wvt PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2wvt 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/2wvt_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.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=2wvt 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)&lt;--&gt;(3)H(4)&lt;--&gt;(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&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 2wvt" 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: Fayers-Kerr J]]
[[Category: Lammerts van Bueren A]]
[[Category: Luo B]]
[[Category: Rovira C]]
[[Category: Sollogoub M]]
[[Category: Zhang Y]]