title: Discovery of Plasmodium vivax N-myristoyltransferase inhibitors: screening, synthesis, and structural characterization of their binding mode.
abstract: N-Myristoyltransferase (NMT) is a prospective drug target against parasitic protozoa. Herein we report the successful discovery of a series of  Plasmodium vivax  NMT inhibitors by high-throughput screening. A high-resolution crystal structure of the hit compound in complex with NMT was obtained, allowing understanding of its novel binding mode. A set of analogues was designed and tested to define the chemical groups relevant for activity and selectivity.
authors.affiliation: Department of Chemistry, Imperial College London, London SW7 2AZ, United Kingdom.
authors.forename: Victor
authors.initials: V
authors.lastname: Goncalves
authors.forename: James A
authors.initials: JA
authors.lastname: Brannigan
authors.forename: David
authors.initials: D
authors.lastname: Whalley
authors.forename: Keith H
authors.initials: KH
authors.lastname: Ansell
authors.forename: Barbara
authors.initials: B
authors.lastname: Saxty
authors.forename: Anthony A
authors.initials: AA
authors.lastname: Holder
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Wilkinson
authors.forename: Edward W
authors.initials: EW
authors.lastname: Tate
authors.forename: Robin J
authors.initials: RJ
authors.lastname: Leatherbarrow
mesh_terms: D000217:Acyltransferases / Q000037:antagonists & inhibitors* / Q000737:chemistry; D000962:Antimalarials / Q000138:chemical synthesis* / Q000737:chemistry; D018360:Crystallography, X-Ray; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000737:chemistry; D008958:Models, Molecular; D015394:Molecular Structure; D010966:Plasmodium vivax / Q000201:enzymology*; D011485:Protein Binding; D011804:Quinolines / Q000138:chemical synthesis* / Q000737:chemistry; D013329:Structure-Activity Relationship
chemical_list: C574654:3-butyl-4-((2-cyanoethyl)thio)-6-methoxy-2-methyl-quinoline; D000962:Antimalarials; D007527:Isoenzymes; D011804:Quinolines; D000217:Acyltransferases; C050480:glycylpeptide N-tetradecanoyltransferase