2yne: Difference between revisions
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==Plasmodium vivax N-myristoyltransferase in complex with a benzothiophene inhibitor== | ==Plasmodium vivax N-myristoyltransferase in complex with a benzothiophene inhibitor== | ||
<StructureSection load='2yne' size='340' side='right' caption='[[2yne]], [[Resolution|resolution]] 1.72Å' scene=''> | <StructureSection load='2yne' size='340' side='right'caption='[[2yne]], [[Resolution|resolution]] 1.72Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[2yne]] is a 3 chain structure with sequence from [ | <table><tr><td colspan='2'>[[2yne]] 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=2YNE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2YNE FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><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>, <scene name='pdbligand=YNE:2-(3-PIPERIDIN-4-YLOXY-1-BENZOTHIOPHEN-2-YL)-5-[(1,3,5-TRIMETHYLPYRAZOL-4-YL)METHYL]-1,3,4-OXADIAZOLE'>YNE</scene | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.72Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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>, <scene name='pdbligand=YNE:2-(3-PIPERIDIN-4-YLOXY-1-BENZOTHIOPHEN-2-YL)-5-[(1,3,5-TRIMETHYLPYRAZOL-4-YL)METHYL]-1,3,4-OXADIAZOLE'>YNE</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=2yne FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2yne OCA], [https://pdbe.org/2yne PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2yne RCSB], [https://www.ebi.ac.uk/pdbsum/2yne PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2yne ProSAT]</span></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | |||
</table> | </table> | ||
== Function == | == 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;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
| Line 24: | Line 23: | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: | [[Category: Plasmodium vivax]] | ||
[[Category: Bottrill | [[Category: Bottrill AR]] | ||
[[Category: Brannigan | [[Category: Brannigan JA]] | ||
[[Category: Broncel | [[Category: Broncel M]] | ||
[[Category: Clough | [[Category: Clough B]] | ||
[[Category: Grainger | [[Category: Grainger M]] | ||
[[Category: Heal | [[Category: Heal WP]] | ||
[[Category: Holder | [[Category: Holder AA]] | ||
[[Category: Leatherbarrow | [[Category: Leatherbarrow RJ]] | ||
[[Category: Mann | [[Category: Mann D]] | ||
[[Category: Rackham | [[Category: Rackham MD]] | ||
[[Category: Serwa | [[Category: Serwa RA]] | ||
[[Category: Tate | [[Category: Tate EW]] | ||
[[Category: Wilkinson | [[Category: Wilkinson AJ]] | ||
[[Category: Wright | [[Category: Wright MH]] | ||
Latest revision as of 17:06, 1 February 2024
Plasmodium vivax N-myristoyltransferase in complex with a benzothiophene inhibitorPlasmodium vivax N-myristoyltransferase in complex with a benzothiophene inhibitor
Structural highlights
FunctionA5K1A2_PLAVS Adds a myristoyl group to the N-terminal glycine residue of certain cellular proteins (By similarity).[RuleBase:RU000586] Publication Abstract from PubMedMalaria is an infectious disease caused by parasites of the genus Plasmodium, which leads to approximately one million deaths per annum worldwide. Chemical validation of new antimalarial targets is urgently required in view of rising resistance to current drugs. One such putative target is the enzyme N-myristoyltransferase, which catalyses the attachment of the fatty acid myristate to protein substrates (N-myristoylation). Here, we report an integrated chemical biology approach to explore protein myristoylation in the major human parasite P. falciparum, combining chemical proteomic tools for identification of the myristoylated and glycosylphosphatidylinositol-anchored proteome with selective small-molecule N-myristoyltransferase inhibitors. We demonstrate that N-myristoyltransferase is an essential and chemically tractable target in malaria parasites both in vitro and in vivo, and show that selective inhibition of N-myristoylation leads to catastrophic and irreversible failure to assemble the inner membrane complex, a critical subcellular organelle in the parasite life cycle. Our studies provide the basis for the development of new antimalarials targeting N-myristoyltransferase. Validation of N-myristoyltransferase as an antimalarial drug target using an integrated chemical biology approach.,Wright MH, Clough B, Rackham MD, Rangachari K, Brannigan JA, Grainger M, Moss DK, Bottrill AR, Heal WP, Broncel M, Serwa RA, Brady D, Mann DJ, Leatherbarrow RJ, Tewari R, Wilkinson AJ, Holder AA, Tate EW Nat Chem. 2014 Feb;6(2):112-21. doi: 10.1038/nchem.1830. Epub 2013 Dec 22. PMID:24451586[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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