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

Summary for 6MAE

• Entry DOI: 10.2210/pdb6mae/pdb
• Descriptor: 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)
• Functional Keywords: lpxc, hydrolase
• Biological source: Pseudomonas aeruginosa (strain ATCC 15692 / DSM 22644 / CIP 104116 / JCM 14847 / LMG 12228 / 1C / PRS 101 / PAO1)
• Total number of polymer chains: 1
• Total formula weight: 33634.54

Authors

Shu, W. (deposition date: 2018-08-27, release date: 2019-01-23, Last modification date: 2024-03-13)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (1.8 Å)