4ad0: Difference between revisions
Jump to navigation
Jump to search
No edit summary |
No edit summary |
||
| Line 1: | Line 1: | ||
==Structure of the GH99 endo-alpha-mannosidase from Bacteriodes thetaiotaomicron in complex with BIS-TRIS-Propane== | |||
<StructureSection load='4ad0' size='340' side='right' caption='[[4ad0]], [[Resolution|resolution]] 2.09Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[4ad0]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Bactn Bactn]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4AD0 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4AD0 FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=B3P:2-[3-(2-HYDROXY-1,1-DIHYDROXYMETHYL-ETHYLAMINO)-PROPYLAMINO]-2-HYDROXYMETHYL-PROPANE-1,3-DIOL'>B3P</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr> | |||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4ad4|4ad4]], [[4acy|4acy]], [[4ad3|4ad3]], [[4ad1|4ad1]], [[4ad2|4ad2]], [[4ad5|4ad5]], [[4acz|4acz]]</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=4ad0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ad0 OCA], [http://pdbe.org/4ad0 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4ad0 RCSB], [http://www.ebi.ac.uk/pdbsum/4ad0 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4ad0 ProSAT]</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®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 4ad0" style="background-color:#fffaf0;"></div> | |||
==See Also== | ==See Also== | ||
*[[Mannosidase|Mannosidase]] | *[[Mannosidase|Mannosidase]] | ||
== References == | |||
== | <references/> | ||
< | __TOC__ | ||
[[Category: | </StructureSection> | ||
[[Category: Bactn]] | |||
[[Category: Glycoprotein endo-alpha-1,2-mannosidase]] | [[Category: Glycoprotein endo-alpha-1,2-mannosidase]] | ||
[[Category: Alonzi, D S | [[Category: Alonzi, D S]] | ||
[[Category: Butters, T D | [[Category: Butters, T D]] | ||
[[Category: Davies, G J | [[Category: Davies, G J]] | ||
[[Category: Gloster, T M | [[Category: Gloster, T M]] | ||
[[Category: Hakki, Z | [[Category: Hakki, Z]] | ||
[[Category: Songsrirote, K | [[Category: Songsrirote, K]] | ||
[[Category: Spreitz, J | [[Category: Spreitz, J]] | ||
[[Category: Stuetz, A E | [[Category: Stuetz, A E]] | ||
[[Category: Thomas-Oates, J E | [[Category: Thomas-Oates, J E]] | ||
[[Category: Thompson, A J | [[Category: Thompson, A J]] | ||
[[Category: Wennekes, T | [[Category: Wennekes, T]] | ||
[[Category: Williams, R J | [[Category: Williams, R J]] | ||
[[Category: Williams, S J | [[Category: Williams, S J]] | ||
[[Category: Wrodnigg, T M | [[Category: Wrodnigg, T M]] | ||
[[Category: Cazy]] | [[Category: Cazy]] | ||
[[Category: Endomannosidase]] | [[Category: Endomannosidase]] | ||
Revision as of 16:30, 19 April 2017
Structure of the GH99 endo-alpha-mannosidase from Bacteriodes thetaiotaomicron in complex with BIS-TRIS-PropaneStructure of the GH99 endo-alpha-mannosidase from Bacteriodes thetaiotaomicron in complex with BIS-TRIS-Propane
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
|
| ||||||||||||||||||||
Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)
OCACategories:
- Bactn
- 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
- Glycoside hydrolase gh99
- Hydrolase
- Mannose glycosidase inhibition