4CYN

Leishmania major N-myristoyltransferase in complex with an aminoacylpyrrolidine inhibitor (2b)

Summary for 4CYN

• Entry DOI: 10.2210/pdb4cyn/pdb
• Related: 4CYO 4CYP 4CYQ
• Descriptor: GLYCYLPEPTIDE N-TETRADECANOYLTRANSFERASE, MAGNESIUM ION, (3R)-3-amino-4-(4-chlorophenyl)-1-[(3R,4S)-3-(4-chlorophenyl)-4-(hydroxymethyl)pyrrolidin-1-yl]butan-1-one, ... (5 entities in total)
• Functional Keywords: transferase, myristoylation, inhibitor, drug design
• Biological source: LEISHMANIA MAJOR
• Total number of polymer chains: 1
• Total formula weight: 48919.66

Authors

Hutton, J.A.,Goncalves, V.,Brannigan, J.A.,Paape, D.,Waugh, T.,Roberts, S.M.,Bell, A.S.,Wilkinson, A.J.,Smith, D.F.,Leatherbarrow, R.J.,Tate, E.W. (deposition date: 2014-04-14, release date: 2014-10-01, Last modification date: 2024-05-08)

Primary citation

Hutton, J.A.,Goncalves, V.,Brannigan, J.A.,Paape, D.,Wright, M.H.,Waugh, T.M.,Roberts, S.M.,Bell, A.S.,Wilkinson, A.J.,Smith, D.F.,Leatherbarrow, R.J.,Tate, E.W.
Structure-Based Design of Potent and Selective Leishmania N- Myristoyltransferase Inhibitors.
J.Med.Chem., 57:8664-, 2014

PubMed Abstract: Inhibitors of Leishmania N-myristoyltransferase (NMT), a potential target for the treatment of leishmaniasis, obtained from a high-throughput screen, were resynthesized to validate activity. Crystal structures bound to Leishmania major NMT were obtained, and the active diastereoisomer of one of the inhibitors was identified. On the basis of structural insights, enzyme inhibition was increased 40-fold through hybridization of two distinct binding modes, resulting in novel, highly potent Leishmania donovani NMT inhibitors with good selectivity over the human enzyme.

PubMed: 25238611
DOI: 10.1021/JM5011397

Experimental method

X-RAY DIFFRACTION (1.4 Å)