View source for 6zdl


==Structure of the catalytic domain of human endo-alpha-mannosidase MANEA in complex with GlcIFG and hexatungstotellurate(VI) TEW==
<StructureSection load='6zdl' size='340' side='right'caption='[[6zdl]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6zdl]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6ZDL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6ZDL 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]] 1.9&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EPE:4-(2-HYDROXYETHYL)-1-PIPERAZINE+ETHANESULFONIC+ACID'>EPE</scene>, <scene name='pdbligand=GLC:ALPHA-D-GLUCOSE'>GLC</scene>, <scene name='pdbligand=IFM:5-HYDROXYMETHYL-3,4-DIHYDROXYPIPERIDINE'>IFM</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=TEW:6-TUNGSTOTELLURATE(VI)'>TEW</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=6zdl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6zdl OCA], [https://pdbe.org/6zdl PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6zdl RCSB], [https://www.ebi.ac.uk/pdbsum/6zdl PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6zdl ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/MANEA_HUMAN MANEA_HUMAN] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Mammalian protein N-linked glycosylation is critical for glycoprotein folding, quality control, trafficking, recognition, and function. N-linked glycans are synthesized from Glc3Man9GlcNAc2 precursors that are trimmed and modified in the endoplasmic reticulum (ER) and Golgi apparatus by glycoside hydrolases and glycosyltransferases. Endo-alpha-1,2-mannosidase (MANEA) is the sole endo-acting glycoside hydrolase involved in N-glycan trimming and is located within the Golgi, where it allows ER-escaped glycoproteins to bypass the classical N-glycosylation trimming pathway involving ER glucosidases I and II. There is considerable interest in the use of small molecules that disrupt N-linked glycosylation as therapeutic agents for diseases such as cancer and viral infection. Here we report the structure of the catalytic domain of human MANEA and complexes with substrate-derived inhibitors, which provide insight into dynamic loop movements that occur on substrate binding. We reveal structural features of the human enzyme that explain its substrate preference and the mechanistic basis for catalysis. These structures have inspired the development of new inhibitors that disrupt host protein N-glycan processing of viral glycans and reduce the infectivity of bovine viral diarrhea and dengue viruses in cellular models. These results may contribute to efforts aimed at developing broad-spectrum antiviral agents and help provide a more in-depth understanding of the biology of mammalian glycosylation.

Structure of human endo-alpha-1,2-mannosidase (MANEA), an antiviral host-glycosylation target.,Sobala LF, Fernandes PZ, Hakki Z, Thompson AJ, Howe JD, Hill M, Zitzmann N, Davies S, Stamataki Z, Butters TD, Alonzi DS, Williams SJ, Davies GJ Proc Natl Acad Sci U S A. 2020 Nov 5. pii: 2013620117. doi:, 10.1073/pnas.2013620117. PMID:33154157<ref>PMID:33154157</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6zdl" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Alonzi DS]]
[[Category: Butters TD]]
[[Category: Davies GJ]]
[[Category: Davies S]]
[[Category: Fernandes PZ]]
[[Category: Hakki Z]]
[[Category: Hill M]]
[[Category: Howe JD]]
[[Category: Sobala LF]]
[[Category: Stamataki Z]]
[[Category: Thompson AJ]]
[[Category: Williams SJ]]
[[Category: Zitzmann N]]