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==Structure of the GH99 endo-alpha-mannosidase from Bacteroides xylanisolvens in complex with glucose-1,3-isofagomine and alpha-1,2- mannobiose== | ==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]] 1.90Å' scene=''> | <StructureSection load='4ad4' size='340' side='right' caption='[[4ad4]], [[Resolution|resolution]] 1.90Å' scene=''> | ||
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<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='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='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> | <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://pdbe.org/4ad4 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4ad4 RCSB], [http://www.ebi.ac.uk/pdbsum/4ad4 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4ad4 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
</div> | </div> | ||
<div class="pdbe-citations 4ad4" style="background-color:#fffaf0;"></div> | |||
== References == | == References == | ||
<references/> | <references/> | ||
Revision as of 16:30, 19 April 2017
Structure of the GH99 endo-alpha-mannosidase from Bacteroides xylanisolvens in complex with glucose-1,3-isofagomine and alpha-1,2- mannobioseStructure of the GH99 endo-alpha-mannosidase from Bacteroides xylanisolvens in complex with glucose-1,3-isofagomine and alpha-1,2- mannobiose
Structural highlights
Publication Abstract from PubMedN-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[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)
OCA- Bacteroides sp. xb1a
- Glycoprotein endo-alpha-1,2-mannosidase
- Alonzi, D S
- Butters, T D
- Davies, G J
- Gloster, T M
- Hakki, Z
- Songsrirote, K
- Spreitz, J
- Stuetz, A E
- Thomas-Oates, J E
- Thompson, A J
- Wennekes, T
- Williams, R J
- Williams, S J
- Wrodnigg, T M
- Cazy
- Endomannosidase
- Enzyme-carbohydrate interaction
- Gh99
- Glycoside hydrolase
- Hydrolase
- Mannose glycosidase inhibition