5N8C

Crystal structure of Pseudomonas aeruginosa LpxC complexed with inhibitor

Summary for 5N8C

• Entry DOI: 10.2210/pdb5n8c/pdb
• Descriptor: UDP-3-O-acyl-N-acetylglucosamine deacetylase, ZINC ION, (2~{S})-3-azanyl-2-[[(1~{R})-5-[2-[4-[[2-(hydroxymethyl)imidazol-1-yl]methyl]phenyl]ethynyl]-2,3-dihydro-1~{H}-inden-1-yl]amino]-3-methyl-~{N}-oxidanyl-butanamide, ... (5 entities in total)
• Functional Keywords: inhibitor, lpxc, hyroxamate, antibacterial, hydrolase
• Biological source: Pseudomonas aeruginosa
• Total number of polymer chains: 2
• Total formula weight: 68371.80

Authors

Cross, J.B.,Ryan, M.D.,Zhang, J.,Cheng, R.K.,Wood, M.,Andersen, O.A.,Brooks, M.,Kwong, J.,Barker, J. (deposition date: 2017-02-23, release date: 2017-03-29, Last modification date: 2024-01-17)

Primary citation

Zhang, J.,Chan, A.,Lippa, B.,Cross, J.B.,Liu, C.,Yin, N.,Romero, J.A.,Lawrence, J.,Heney, R.,Herradura, P.,Goss, J.,Clark, C.,Abel, C.,Zhang, Y.,Poutsiaka, K.M.,Epie, F.,Conrad, M.,Mahamoon, A.,Nguyen, K.,Chavan, A.,Clark, E.,Li, T.C.,Cheng, R.K.,Wood, M.,Andersen, O.A.,Brooks, M.,Kwong, J.,Barker, J.,Parr, I.B.,Gu, Y.,Ryan, M.D.,Coleman, S.,Metcalf, C.A.
Structure-based discovery of LpxC inhibitors.
Bioorg. Med. Chem. Lett., 27:1670-1680, 2017

PubMed Abstract: The emergence and spread of multidrug-resistant (MDR) Gram negative bacteria presents a serious threat for public health. Novel antimicrobials that could overcome the resistance problems are urgently needed. UDP-3-O-(R-3-hydroxymyristol)-N-acetylglucosamine deacetylase (LpxC) is a cytosolic zinc-based deacetylase that catalyzes the first committed step in the biosynthesis of lipid A, which is essential for the survival of Gram-negative bacteria. Our efforts toward the discovery of novel LpxC inhibitors are presented herein.

PubMed: 28302397
DOI: 10.1016/j.bmcl.2017.03.006

Experimental method

X-RAY DIFFRACTION (1.9 Å)