title: New developments in probing and targeting protein acylation in malaria, leishmaniasis and African sleeping sickness.
abstract: Infections by protozoan parasites, such as Plasmodium falciparum or Leishmania donovani, have a significant health, social and economic impact and threaten billions of people living in tropical and sub-tropical regions of developing countries worldwide. The increasing range of parasite strains resistant to frontline therapeutics makes the identification of novel drug targets and the development of corresponding inhibitors vital. Post-translational modifications (PTMs) are important modulators of biology and inhibition of protein lipidation has emerged as a promising therapeutic strategy for treatment of parasitic diseases. In this review we summarize the latest insights into protein lipidation in protozoan parasites. We discuss how recent chemical proteomic approaches have delivered the first global overviews of protein lipidation in these organisms, contributing to our understanding of the role of this PTM in critical metabolic and cellular functions. Additionally, we highlight the development of new small molecule inhibitors to target parasite acyl transferases.
authors.affiliation: Department of Chemistry,Imperial College London,London SW7 2AZ,UK.
authors.forename: Markus
authors.identifier: 0000-0002-9898-4110
authors.initials: M
authors.lastname: Ritzefeld
authors.affiliation: School of Chemistry, University of Leeds,Leeds LS2 9JT,UK.
authors.forename: Megan H
authors.initials: MH
authors.lastname: Wright
authors.affiliation: Department of Chemistry,Imperial College London,London SW7 2AZ,UK.
authors.forename: Edward W
authors.initials: EW
authors.lastname: Tate
mesh_terms: D000215:Acylation / Q000187:drug effects; D016503:Drug Delivery Systems / Q000379:methods*; D006801:Humans; D007893:Leishmania donovani / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D007896:Leishmaniasis / Q000188:drug therapy; D016778:Malaria, Falciparum / Q000188:drug therapy; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D021381:Protein Transport; D040901:Proteomics / Q000379:methods; D015800:Protozoan Proteins / Q000378:metabolism*; D014166:Transferases / Q000037:antagonists & inhibitors / Q000187:drug effects; D014353:Trypanosomiasis, African / Q000188:drug therapy / Q000469:parasitology
chemical_list: D015800:Protozoan Proteins; D014166:Transferases
keywords: 
                 N-myristoyl transferase; NMT; acyl transferase; palmitoylation; post-translational modification; protein lipidation; proteomics; protozoan parasites; small molecule inhibitor