4ad4: Difference between revisions
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<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=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[4ad4]] is a 1 chain structure | <table><tr><td colspan='2'>[[4ad4]] is a 1 chain structure. 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 [https://proteopedia.org/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> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[4ad3|4ad3]], [[4ad1|4ad1]], [[4ad2|4ad2]], [[4ad5|4ad5]], [[4acy|4acy]], [[4acz|4acz]], [[4ad0|4ad0]]</div></td></tr> | ||
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[ | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Glycoprotein_endo-alpha-1,2-mannosidase Glycoprotein endo-alpha-1,2-mannosidase], with EC number [https://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'>[ | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4ad4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ad4 OCA], [https://pdbe.org/4ad4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4ad4 RCSB], [https://www.ebi.ac.uk/pdbsum/4ad4 PDBsum], [https://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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==See Also== | ==See Also== | ||
*[[Mannosidase|Mannosidase]] | *[[Mannosidase 3D structures|Mannosidase 3D structures]] | ||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Glycoprotein endo-alpha-1,2-mannosidase]] | [[Category: Glycoprotein endo-alpha-1,2-mannosidase]] | ||
[[Category: Large Structures]] | |||
[[Category: Alonzi, D S]] | [[Category: Alonzi, D S]] | ||
[[Category: Butters, T D]] | [[Category: Butters, T D]] | ||
Revision as of 08:30, 25 August 2022
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. See AlsoReferences
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Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)
OCA- Glycoprotein endo-alpha-1,2-mannosidase
- Large Structures
- 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