4CYN

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

4CYN の概要

• エントリーDOI: 10.2210/pdb4cyn/pdb
• 関連するPDBエントリー: 4CYO 4CYP 4CYQ
• 分子名称: 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)
• 機能のキーワード: transferase, myristoylation, inhibitor, drug design
• 由来する生物種: LEISHMANIA MAJOR
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 48919.66

構造登録者

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. (登録日: 2014-04-14, 公開日: 2014-10-01, 最終更新日: 2024-05-08)

主引用文献

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

実験手法

X-RAY DIFFRACTION (1.4 Å)