5T6C

Crystal structure of Aspergillus fumigatus N-myristoyl transferase in complex with myristoyl CoA and a dichloro-methylpyridinyl-methoxy-phenyl-pyridine piperazine ligand

Summary for 5T6C

• Entry DOI: 10.2210/pdb5t6c/pdb
• Descriptor: Glycylpeptide N-tetradecanoyltransferase, TETRADECANOYL-COA, 1-(4-{3,5-dichloro-4-[(2-methylpyridin-3-yl)methoxy]phenyl}pyridin-2-yl)piperazine, ... (4 entities in total)
• Functional Keywords: acyltransferase, transferase, drug discovery
• Biological source: Neosartorya fumigata (strain ATCC MYA-4609 / Af293 / CBS 101355 / FGSC A1100)
• Total number of polymer chains: 1
• Total formula weight: 48850.48

Authors

Robinson, D.A.,Wyatt, P.G. (deposition date: 2016-09-01, release date: 2017-09-13, Last modification date: 2024-01-17)

Primary citation

Bayliss, T.,Robinson, D.A.,Smith, V.C.,Brand, S.,McElroy, S.P.,Torrie, L.S.,Mpamhanga, C.,Norval, S.,Stojanovski, L.,Brenk, R.,Frearson, J.A.,Read, K.D.,Gilbert, I.H.,Wyatt, P.G.
Design and Synthesis of Brain Penetrant Trypanocidal N-Myristoyltransferase Inhibitors.
J. Med. Chem., 60:9790-9806, 2017

PubMed Abstract: N-Myristoyltransferase (NMT) represents a promising drug target within the parasitic protozoa Trypanosoma brucei (T. brucei), the causative agent for human African trypanosomiasis (HAT) or sleeping sickness. We have previously validated T. brucei NMT as a promising druggable target for the treatment of HAT in both stages 1 and 2 of the disease. We report on the use of the previously reported DDD85646 (1) as a starting point for the design of a class of potent, brain penetrant inhibitors of T. brucei NMT.

PubMed: 29125744
DOI: 10.1021/acs.jmedchem.7b01255

Experimental method

X-RAY DIFFRACTION (1.9 Å)