2ync

Plasmodium vivax N-myristoyltransferase in complex with YnC12-CoA thioester.

spinqualitylabelsall models 2ync, resolution 1.75Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 2ync is a 3 chain structure with sequence from Haemamoeba vivax. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: CL, DMS, MG, SO4, YNC Related: 4a95, 4b10, 4b11, 4b12, 4b13, 4b14, 4bbh, 2ynd, 2yne Activity: Glycylpeptide N-tetradecanoyltransferase, with EC number 2.3.1.97 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [A5K1A2_PLAVS] Adds a myristoyl group to the N-terminal glycine residue of certain cellular proteins (By similarity).[RuleBase:RU000586] Publication Abstract from PubMed Malaria 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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