View source for 4v27


==Structure of the GH99 endo-alpha-mannanase from Bacteroides xylanisolvens in complex with mannose-alpha-1,3-isofagomine==
<StructureSection load='4v27' size='340' side='right'caption='[[4v27]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4v27]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Bacteroides_xylanisolvens_XB1A Bacteroides xylanisolvens XB1A]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4V27 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4V27 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]] 1.9&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=IFM:5-HYDROXYMETHYL-3,4-DIHYDROXYPIPERIDINE'>IFM</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</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=4v27 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4v27 OCA], [https://pdbe.org/4v27 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4v27 RCSB], [https://www.ebi.ac.uk/pdbsum/4v27 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4v27 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/D6D1V7_9BACE D6D1V7_9BACE] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Glycoside hydrolase family 99 (GH99) was created to categorize sequence-related glycosidases possessing endo-alpha-mannosidase activity: the cleavage of mannosidic linkages within eukaryotic N-glycan precursors (Glc1-3 Man9 GlcNAc2 ), releasing mono-, di- and triglucosylated-mannose (Glc1-3 -1,3-Man). GH99 family members have recently been implicated in the ability of Bacteroides spp., present within the gut microbiota, to metabolize fungal cell wall alpha-mannans, releasing alpha-1,3-mannobiose by hydrolysing alphaMan-1,3-alphaMan--&gt;1,2-alphaMan-1,2-alphaMan sequences within branches off the main alpha-1,6-mannan backbone. We report the development of a series of substrates and inhibitors, which we use to kinetically and structurally characterise this novel endo-alpha-1,2-mannanase activity of bacterial GH99 enzymes from Bacteroides thetaiotaomicron and xylanisolvens. These data reveal an approximate 5 kJ mol-1 preference for mannose-configured substrates in the -2 subsite (relative to glucose), which inspired the development of a new inhibitor, alpha-mannopyranosyl-1,3-isofagomine (ManIFG), the most potent (bacterial) GH99 inhibitor reported to date. X-ray structures of ManIFG or a substrate in complex with wild-type or inactive mutants, respectively, of B. xylanisolvens GH99 reveal the structural basis for binding to D-mannose- rather than D-glucose-configured substrates.

Structural and Kinetic Dissection of the endo-alpha-1,2-Mannanase Activity of Bacterial GH99 Glycoside Hydrolases from Bacteroides spp.,Hakki Z, Thompson AJ, Bellmaine S, Speciale G, Davies GJ, Williams SJ Chemistry. 2014 Dec 8. doi: 10.1002/chem.201405539. PMID:25487964<ref>PMID:25487964</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4v27" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Bacteroides xylanisolvens XB1A]]
[[Category: Large Structures]]
[[Category: Bellmaine S]]
[[Category: Davies GJ]]
[[Category: Hakki Z]]
[[Category: Speciale G]]
[[Category: Thompson AJ]]
[[Category: Williams SJ]]