5o48: Difference between revisions

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New page: '''Unreleased structure''' The entry 5o48 is ON HOLD Authors: Brannigan, J.A., Wilkinson, A.J. Description: P.vivax NMT with an aminomethylindazole inhibitor bound [[Category: Unreleas...
 
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'''Unreleased structure'''


The entry 5o48 is ON HOLD
==P.vivax NMT with an aminomethylindazole inhibitor bound==
<StructureSection load='5o48' size='340' side='right'caption='[[5o48]], [[Resolution|resolution]] 1.69&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5o48]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Plasmodium_vivax Plasmodium vivax]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5O48 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5O48 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=9K2:1-[5-(4-fluoranyl-2-methyl-phenyl)-1~{H}-indazol-3-yl]-~{N},~{N}-dimethyl-methanamine'>9K2</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=NHW:2-OXOPENTADECYL-COA'>NHW</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=5o48 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5o48 OCA], [https://pdbe.org/5o48 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5o48 RCSB], [https://www.ebi.ac.uk/pdbsum/5o48 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5o48 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/A5K1A2_PLAVS A5K1A2_PLAVS] Adds a myristoyl group to the N-terminal glycine residue of certain cellular proteins (By similarity).[RuleBase:RU000586]
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Rhinoviruses (RVs) are the pathogens most often responsible for the common cold, and are a frequent cause of exacerbations in asthma, chronic obstructive pulmonary disease and cystic fibrosis. Here we report the discovery of IMP-1088, a picomolar dual inhibitor of the human N-myristoyltransferases NMT1 and NMT2, and use it to demonstrate that pharmacological inhibition of host-cell N-myristoylation rapidly and completely prevents rhinoviral replication without inducing cytotoxicity. The identification of cooperative binding between weak-binding fragments led to rapid inhibitor optimization through fragment reconstruction, structure-guided fragment linking and conformational control over linker geometry. We show that inhibition of the co-translational myristoylation of a specific virus-encoded protein (VP0) by IMP-1088 potently blocks a key step in viral capsid assembly, to deliver a low nanomolar antiviral activity against multiple RV strains, poliovirus and foot and-mouth disease virus, and protection of cells against virus-induced killing, highlighting the potential of host myristoylation as a drug target in picornaviral infections.


Authors: Brannigan, J.A., Wilkinson, A.J.
Fragment-derived inhibitors of human N-myristoyltransferase block capsid assembly and replication of the common cold virus.,Mousnier A, Bell AS, Swieboda DP, Morales-Sanfrutos J, Perez-Dorado I, Brannigan JA, Newman J, Ritzefeld M, Hutton JA, Guedan A, Asfor AS, Robinson SW, Hopkins-Navratilova I, Wilkinson AJ, Johnston SL, Leatherbarrow RJ, Tuthill TJ, Solari R, Tate EW Nat Chem. 2018 May 14. pii: 10.1038/s41557-018-0039-2. doi:, 10.1038/s41557-018-0039-2. PMID:29760414<ref>PMID:29760414</ref>


Description: P.vivax NMT with an aminomethylindazole inhibitor bound
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
[[Category: Unreleased Structures]]
</div>
[[Category: Wilkinson, A.J]]
<div class="pdbe-citations 5o48" style="background-color:#fffaf0;"></div>
[[Category: Brannigan, J.A]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Plasmodium vivax]]
[[Category: Brannigan JA]]
[[Category: Wilkinson AJ]]
Retrieved from "https://proteopedia.org/5o48"