View source for 4ad4

==Structure of the GH99 endo-alpha-mannosidase from Bacteroides xylanisolvens in complex with glucose-1,3-isofagomine and alpha-1,2- mannobiose==
<StructureSection load='4ad4' size='340' side='right' caption='[[4ad4]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4ad4]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Bacteroides_sp._xb1a Bacteroides sp. xb1a]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4AD4 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4AD4 FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GLC:ALPHA-D-GLUCOSE'>GLC</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='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4ad3|4ad3]], [[4ad1|4ad1]], [[4ad2|4ad2]], [[4ad5|4ad5]], [[4acy|4acy]], [[4acz|4acz]], [[4ad0|4ad0]]</td></tr>
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Glycoprotein_endo-alpha-1,2-mannosidase Glycoprotein endo-alpha-1,2-mannosidase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.2.1.130 3.2.1.130] </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=4ad4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ad4 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4ad4 RCSB], [http://www.ebi.ac.uk/pdbsum/4ad4 PDBsum]</span></td></tr>
</table>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
N-linked glycans play key roles in protein folding, stability, and function. Biosynthetic modification of N-linked glycans, within the endoplasmic reticulum, features sequential trimming and readornment steps. One unusual enzyme, endo-alpha-mannosidase, cleaves mannoside linkages internally within an N-linked glycan chain, short circuiting the classical N-glycan biosynthetic pathway. Here, using two bacterial orthologs, we present the first structural and mechanistic dissection of endo-alpha-mannosidase. Structures solved at resolutions 1.7-2.1 A reveal a (beta/alpha)(8) barrel fold in which the catalytic center is present in a long substrate-binding groove, consistent with cleavage within the N-glycan chain. Enzymatic cleavage of authentic Glc(1/3)Man(9)GlcNAc(2) yields Glc(1/3)-Man. Using the bespoke substrate alpha-Glc-1,3-alpha-Man fluoride, the enzyme was shown to act with retention of anomeric configuration. Complexes with the established endo-alpha-mannosidase inhibitor alpha-Glc-1,3-deoxymannonojirimycin and a newly developed inhibitor, alpha-Glc-1,3-isofagomine, and with the reducing-end product alpha-1,2-mannobiose structurally define the -2 to +2 subsites of the enzyme. These structural and mechanistic data provide a foundation upon which to develop new enzyme inhibitors targeting the hijacking of N-glycan synthesis in viral disease and cancer.

Structural and mechanistic insight into N-glycan processing by endo-alpha-mannosidase.,Thompson AJ, Williams RJ, Hakki Z, Alonzi DS, Wennekes T, Gloster TM, Songsrirote K, Thomas-Oates JE, Wrodnigg TM, Spreitz J, Stutz AE, Butters TD, Williams SJ, Davies GJ Proc Natl Acad Sci U S A. 2012 Jan 4. PMID:22219371<ref>PMID:22219371</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Bacteroides sp. xb1a]]
[[Category: Glycoprotein endo-alpha-1,2-mannosidase]]
[[Category: Alonzi, D S]]
[[Category: Butters, T D]]
[[Category: Davies, G J]]
[[Category: Gloster, T M]]
[[Category: Hakki, Z]]
[[Category: Songsrirote, K]]
[[Category: Spreitz, J]]
[[Category: Stuetz, A E]]
[[Category: Thomas-Oates, J E]]
[[Category: Thompson, A J]]
[[Category: Wennekes, T]]
[[Category: Williams, R J]]
[[Category: Williams, S J]]
[[Category: Wrodnigg, T M]]
[[Category: Cazy]]
[[Category: Endomannosidase]]
[[Category: Enzyme-carbohydrate interaction]]
[[Category: Gh99]]
[[Category: Glycoside hydrolase]]
[[Category: Hydrolase]]
[[Category: Mannose glycosidase inhibition]]