3P3E

Crystal Structure of the PSEUDOMONAS AERUGINOSA LpxC/LPC-009 complex

Summary for 3P3E

• Entry DOI: 10.2210/pdb3p3e/pdb
• Related: 2VES 3P3C 3P3G
• Descriptor: UDP-3-O-[3-hydroxymyristoyl] N-acetylglucosamine deacetylase, ZINC ION, N-[(1S,2R)-2-hydroxy-1-(hydroxycarbamoyl)propyl]-4-(4-phenylbuta-1,3-diyn-1-yl)benzamide, ... (6 entities in total)
• Functional Keywords: lipid a biosynthesis, lipid a synthesis, lpxc, baab sandwich, hydrolase, deacetylation, antibiotic, acyl udp-glcnac, hydroxamate, lpc-009
• Biological source: Pseudomonas aeruginosa
• Total number of polymer chains: 1
• Total formula weight: 35212.93

Authors

Lee, C.-J.,Zhou, P. (deposition date: 2010-10-04, release date: 2011-01-05, Last modification date: 2024-02-21)

Primary citation

Lee, C.J.,Liang, X.,Chen, X.,Zeng, D.,Joo, S.H.,Chung, H.S.,Barb, A.W.,Swanson, S.M.,Nicholas, R.A.,Li, Y.,Toone, E.J.,Raetz, C.R.,Zhou, P.
Species-specific and inhibitor-dependent conformations of LpxC: implications for antibiotic design.
Chem.Biol., 18:38-47, 2011

PubMed Abstract: LpxC is an essential enzyme in the lipid A biosynthetic pathway in gram-negative bacteria. Several promising antimicrobial lead compounds targeting LpxC have been reported, though they typically display a large variation in potency against different gram-negative pathogens. We report that inhibitors with a diacetylene scaffold effectively overcome the resistance caused by sequence variation in the LpxC substrate-binding passage. Compound binding is captured in complex with representative LpxC orthologs, and structural analysis reveals large conformational differences that mostly reflect inherent molecular features of distinct LpxC orthologs, whereas ligand-induced structural adaptations occur at a smaller scale. These observations highlight the need for a molecular understanding of inherent structural features and conformational plasticity of LpxC enzymes for optimizing LpxC inhibitors as broad-spectrum antibiotics against gram-negative infections.

PubMed: 21167751
DOI: 10.1016/j.chembiol.2010.11.011

Experimental method

X-RAY DIFFRACTION (1.28 Å)