PDBsum entry 4ucn

Transferase

PDB id: 4ucn

Contents

Protein chain

411 a.a.

Ligands

JRB

MYA

Waters ×324

References listed in PDB file

Key reference

• Title: Identification and structure solution of fragment hits against kinetoplastid n-Myristoyltransferase.
• Authors: D.A.Robinson, P.G.Wyatt.
• Ref.: Acta Crystallogr F Struct Biol Commun, 2015, 71, 586-593. [DOI no: 10.1107/S2053230X15003040]
• PubMed id: 25945713

Abstract

Trypanosoma 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.