5yzc: Difference between revisions
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<StructureSection load='5yzc' size='340' side='right' caption='[[5yzc]], [[Resolution|resolution]] 2.33Å' scene=''> | <StructureSection load='5yzc' size='340' side='right' caption='[[5yzc]], [[Resolution|resolution]] 2.33Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[5yzc]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5YZC OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5YZC FirstGlance]. <br> | <table><tr><td colspan='2'>[[5yzc]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Measc Measc]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5YZC OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5YZC FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=95C:4-nitro-2-[(phenylacetyl)amino]benzamide'>95C</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=95C:4-nitro-2-[(phenylacetyl)amino]benzamide'>95C</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr> | ||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5yxw|5yxw]]</td></tr> | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5yxw|5yxw]]</td></tr> | ||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">F ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=645098 MEASC])</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=5yzc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5yzc OCA], [http://pdbe.org/5yzc PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5yzc RCSB], [http://www.ebi.ac.uk/pdbsum/5yzc PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5yzc ProSAT]</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=5yzc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5yzc OCA], [http://pdbe.org/5yzc PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5yzc RCSB], [http://www.ebi.ac.uk/pdbsum/5yzc PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5yzc ProSAT]</span></td></tr> | ||
</table> | </table> | ||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Measles virus (MeV), a major cause of childhood morbidity and mortality, is highly immunotropic and one of the most contagious pathogens. MeV may establish, albeit rarely, persistent infection in the central nervous system, causing fatal and intractable neurodegenerative diseases such as subacute sclerosing panencephalitis and measles inclusion body encephalitis. Recent studies have suggested that particular substitutions in the MeV fusion (F) protein are involved in the pathogenesis by destabilizing the F protein and endowing it with hyperfusogenicity. Here we show the crystal structures of the prefusion MeV-F alone and in complex with the small compound AS-48 or a fusion inhibitor peptide. Notably, these independently developed inhibitors bind the same hydrophobic pocket located at the region connecting the head and stalk of MeV-F, where a number of substitutions in MeV isolates from neurodegenerative diseases are also localized. Since these inhibitors could suppress membrane fusion mediated by most of the hyperfusogenic MeV-F mutants, the development of more effective inhibitors based on the structures may be warranted to treat MeV-induced neurodegenerative diseases. | |||
Structures of the prefusion form of measles virus fusion protein in complex with inhibitors.,Hashiguchi T, Fukuda Y, Matsuoka R, Kuroda D, Kubota M, Shirogane Y, Watanabe S, Tsumoto K, Kohda D, Plemper RK, Yanagi Y Proc Natl Acad Sci U S A. 2018 Mar 6;115(10):2496-2501. doi:, 10.1073/pnas.1718957115. Epub 2018 Feb 20. PMID:29463726<ref>PMID:29463726</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 5yzc" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Measc]] | |||
[[Category: Fukuda, Y]] | [[Category: Fukuda, Y]] | ||
[[Category: Hashiguchi, T]] | [[Category: Hashiguchi, T]] | ||
Revision as of 09:19, 8 March 2018
Crystal structure of the prefusion form of measles virus fusion protein in complex with a fusion inhibitor compound (AS-48)Crystal structure of the prefusion form of measles virus fusion protein in complex with a fusion inhibitor compound (AS-48)
Structural highlights
Publication Abstract from PubMedMeasles virus (MeV), a major cause of childhood morbidity and mortality, is highly immunotropic and one of the most contagious pathogens. MeV may establish, albeit rarely, persistent infection in the central nervous system, causing fatal and intractable neurodegenerative diseases such as subacute sclerosing panencephalitis and measles inclusion body encephalitis. Recent studies have suggested that particular substitutions in the MeV fusion (F) protein are involved in the pathogenesis by destabilizing the F protein and endowing it with hyperfusogenicity. Here we show the crystal structures of the prefusion MeV-F alone and in complex with the small compound AS-48 or a fusion inhibitor peptide. Notably, these independently developed inhibitors bind the same hydrophobic pocket located at the region connecting the head and stalk of MeV-F, where a number of substitutions in MeV isolates from neurodegenerative diseases are also localized. Since these inhibitors could suppress membrane fusion mediated by most of the hyperfusogenic MeV-F mutants, the development of more effective inhibitors based on the structures may be warranted to treat MeV-induced neurodegenerative diseases. Structures of the prefusion form of measles virus fusion protein in complex with inhibitors.,Hashiguchi T, Fukuda Y, Matsuoka R, Kuroda D, Kubota M, Shirogane Y, Watanabe S, Tsumoto K, Kohda D, Plemper RK, Yanagi Y Proc Natl Acad Sci U S A. 2018 Mar 6;115(10):2496-2501. doi:, 10.1073/pnas.1718957115. Epub 2018 Feb 20. PMID:29463726[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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