4acy: Difference between revisions

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-[[Image:4acy.png|left|200px]]
-{{STRUCTURE_4acy|  PDB=4acy  |  SCENE=  }}
+==Selenomethionine derivative of the GH99 endo-alpha-mannosidase from Bacteroides thetaiotaomicron==
+<StructureSection load='4acy' size='340' side='right'caption='[[4acy]], [[Resolution|resolution]] 1.69&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[4acy]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Bacteroides_thetaiotaomicron_VPI-5482 Bacteroides thetaiotaomicron VPI-5482]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4ACY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4ACY 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]] 1.69&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FMT:FORMIC+ACID'>FMT</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</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=4acy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4acy OCA], [https://pdbe.org/4acy PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4acy RCSB], [https://www.ebi.ac.uk/pdbsum/4acy PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4acy ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/Q8A109_BACTN Q8A109_BACTN]
+<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.
-===Selenomethionine derivative of the GH99 endo-alpha-mannosidase from Bacteroides thetaiotaomicron===
+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>
-{{ABSTRACT_PUBMED_22219371}}
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
-==About this Structure==
+<div class="pdbe-citations 4acy" style="background-color:#fffaf0;"></div>
-[[4acy]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Bacteroides_thetaiotaomicron Bacteroides thetaiotaomicron]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4ACY OCA].
 ==See Also==
-*[[Mannosidase|Mannosidase]]
+*[[Mannosidase 3D structures|Mannosidase 3D structures]]
+== References ==
-==Reference==
+<references/>
-<ref group="xtra">PMID:022219371</ref><references group="xtra"/>
+__TOC__
-[[Category: Bacteroides thetaiotaomicron]]
+</StructureSection>
-[[Category: Glycoprotein endo-alpha-1,2-mannosidase]]
+[[Category: Bacteroides thetaiotaomicron VPI-5482]]
-[[Category: Alonzi, D S.]]
+[[Category: Large Structures]]
-[[Category: Butters, T D.]]
+[[Category: Alonzi DS]]
-[[Category: Davies, G J.]]
+[[Category: Butters TD]]
-[[Category: Gloster, T M.]]
+[[Category: Davies GJ]]
-[[Category: Hakki, Z.]]
+[[Category: Gloster TM]]
-[[Category: Songsrirote, K.]]
+[[Category: Hakki Z]]
-[[Category: Spreitz, J.]]
+[[Category: Songsrirote K]]
-[[Category: Stuetz, A E.]]
+[[Category: Spreitz J]]
-[[Category: Thomas-Oates, J E.]]
+[[Category: Stuetz AE]]
-[[Category: Thompson, A J.]]
+[[Category: Thomas-Oates JE]]
-[[Category: Wennekes, T.]]
+[[Category: Thompson AJ]]
-[[Category: Williams, R J.]]
+[[Category: Wennekes T]]
-[[Category: Williams, S J.]]
+[[Category: Williams RJ]]
-[[Category: Wrodnigg, T M.]]
+[[Category: Williams SJ]]
-[[Category: Cazy]]
+[[Category: Wrodnigg TM]]
-[[Category: Endomannosidase]]
-[[Category: Enzyme-carbohydrate interaction]]
-[[Category: Glycosidase inhibition]]
-[[Category: Glycoside hydrolase]]
-[[Category: Hydrolase]]
-[[Category: Mannose]]