6zdf: Difference between revisions
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<StructureSection load='6zdf' size='340' side='right'caption='[[6zdf]], [[Resolution|resolution]] 3.00Å' scene=''> | <StructureSection load='6zdf' size='340' side='right'caption='[[6zdf]], [[Resolution|resolution]] 3.00Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[6zdf]] is a 3 chain structure with sequence from [ | <table><tr><td colspan='2'>[[6zdf]] is a 3 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=6ZDF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6ZDF FirstGlance]. <br> | ||
</td></tr><tr id=' | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3Å</td></tr> | ||
<tr id=' | <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></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=6zdf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6zdf OCA], [https://pdbe.org/6zdf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6zdf RCSB], [https://www.ebi.ac.uk/pdbsum/6zdf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6zdf ProSAT]</span></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | |||
</table> | </table> | ||
== Function == | |||
[https://www.uniprot.org/uniprot/MANEA_HUMAN MANEA_HUMAN] | |||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
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</div> | </div> | ||
<div class="pdbe-citations 6zdf" style="background-color:#fffaf0;"></div> | <div class="pdbe-citations 6zdf" style="background-color:#fffaf0;"></div> | ||
==See Also== | |||
*[[Mannosidase 3D structures|Mannosidase 3D structures]] | |||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Homo sapiens]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Alonzi | [[Category: Alonzi DS]] | ||
[[Category: Butters | [[Category: Butters TD]] | ||
[[Category: Davies | [[Category: Davies GJ]] | ||
[[Category: Davies | [[Category: Davies S]] | ||
[[Category: Fernandes | [[Category: Fernandes PZ]] | ||
[[Category: Hakki | [[Category: Hakki Z]] | ||
[[Category: Hill | [[Category: Hill M]] | ||
[[Category: Howe | [[Category: Howe JD]] | ||
[[Category: Sobala | [[Category: Sobala LF]] | ||
[[Category: Stamataki | [[Category: Stamataki Z]] | ||
[[Category: Thompson | [[Category: Thompson AJ]] | ||
[[Category: Williams | [[Category: Williams SJ]] | ||
[[Category: Zitzmann | [[Category: Zitzmann N]] | ||
Latest revision as of 16:47, 24 January 2024
Structure of the catalytic domain of human endo-alpha-mannosidase MANEA in complex with HEPESStructure of the catalytic domain of human endo-alpha-mannosidase MANEA in complex with HEPES
Structural highlights
FunctionPublication Abstract from PubMedMammalian 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[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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