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CRYSTAL STRUCTURE OF LEISHMANIA MAJOR N-MYRISTOYLTRANSFERASE (NMT) WITH BOUND MYRISTOYL-COA AND A FRAGMENTCRYSTAL STRUCTURE OF LEISHMANIA MAJOR N-MYRISTOYLTRANSFERASE (NMT) WITH BOUND MYRISTOYL-COA AND A FRAGMENT
Structural highlights
FunctionQ4Q5S8_LEIMA Adds a myristoyl group to the N-terminal glycine residue of certain cellular proteins (By similarity). Publication Abstract from PubMedTrypanosoma brucei N-myristoyltransferase (TbNMT) is an attractive therapeutic target for the treatment of human African trypanosomiasis. Pyrazole sulfonamide (DDD85646), a potent inhibitor of TbNMT, has been identified in previous studies; however, poor central nervous system exposure restricts its use to the haemolymphatic form (stage 1) of the disease. In order to identify new chemical matter, a fragment screen was carried out by ligand-observed NMR spectroscopy, identifying hits that occupy the DDD85646 binding site. Crystal structures of hits from this assay have been obtained in complex with the closely related NMT from Leishmania major, providing a structural starting point for the evolution of novel chemical matter. Identification and structure solution of fragment hits against kinetoplastid N-myristoyltransferase.,Robinson DA, Wyatt PG Acta Crystallogr F Struct Biol Commun. 2015 May;71(Pt 5):586-93. doi:, 10.1107/S2053230X15003040. Epub 2015 Apr 21. PMID:25945713[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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