6MAE

CHAIN A. UDP-3-O-[3-hydroxymyristoyl] N-acetylglucosamine deacetylase PA-LPXC Complexed with (R)-3-((S)-3-(4-(cyclopropylethynyl)phenyl)-2-oxooxazolidin-5-yl)-N-hydroxy-2-methyl-2-(methylsulfonyl)propenamide

6MAE の概要

• エントリーDOI: 10.2210/pdb6mae/pdb
• 分子名称: UDP-3-O-acyl-N-acetylglucosamine deacetylase, (2R)-3-{(5S)-3-[4-(cyclopropylethynyl)phenyl]-2-oxo-1,3-oxazolidin-5-yl}-N-hydroxy-2-methyl-2-(methylsulfonyl)propanamide, ZINC ION, ... (4 entities in total)
• 機能のキーワード: lpxc, hydrolase
• 由来する生物種: Pseudomonas aeruginosa (strain ATCC 15692 / DSM 22644 / CIP 104116 / JCM 14847 / LMG 12228 / 1C / PRS 101 / PAO1)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 33634.54

構造登録者

Shu, W. (登録日: 2018-08-27, 公開日: 2019-01-23, 最終更新日: 2024-03-13)

主引用文献

Lee, P.S.,Lapointe, G.,Madera, A.M.,Simmons, R.L.,Xu, W.,Yifru, A.,Tjandra, M.,Karur, S.,Rico, A.,Thompson, K.,Bojkovic, J.,Xie, L.,Uehara, K.,Liu, A.,Shu, W.,Bellamacina, C.,McKenney, D.,Morris, L.,Tonn, G.R.,Osborne, C.,Benton, B.M.,McDowell, L.,Fu, J.,Sweeney, Z.K.
Application of Virtual Screening to the Identification of New LpxC Inhibitor Chemotypes, Oxazolidinone and Isoxazoline.
J. Med. Chem., 61:9360-9370, 2018

PubMed Abstract: This report summarizes the identification and synthesis of novel LpxC inhibitors aided by computational methods that leveraged numerous crystal structures. This effort led to the identification of oxazolidinone and isoxazoline inhibitors with potent in vitro activity against P. aeruginosa and other Gram-negative bacteria. Representative compound 13f demonstrated efficacy against P. aeruginosa in a mouse neutropenic thigh infection model. The antibacterial activity against K. pneumoniae could be potentiated by Gram-positive antibiotics rifampicin (RIF) and vancomycin (VAN) in both in vitro and in vivo models.

PubMed: 30226381
DOI: 10.1021/acs.jmedchem.8b01287

実験手法

X-RAY DIFFRACTION (1.8 Å)