5B4C

Crystal structure of H10N mutant of LpxH with manganese

Summary for 5B4C

• Entry DOI: 10.2210/pdb5b4c/pdb
• Related: 5B49 5B4A 5B4B 5B4D
• Descriptor: UDP-2,3-diacylglucosamine hydrolase, MANGANESE (II) ION, GLYCEROL, ... (4 entities in total)
• Functional Keywords: lpxh, lipid a, lipid x, udp-2, 3-diacylglucosamine, hydrolase
• Biological source: Pseudomonas aeruginosa PAO1
• Total number of polymer chains: 2
• Total formula weight: 57772.03

Authors

Okada, C.,Wakabayashi, H.,Yao, M.,Tanaka, I. (deposition date: 2016-04-03, release date: 2016-09-28, Last modification date: 2023-11-08)

Primary citation

Okada, C.,Wakabayashi, H.,Kobayashi, M.,Shinoda, A.,Tanaka, I.,Yao, M.
Crystal structures of the UDP-diacylglucosamine pyrophosphohydrase LpxH from Pseudomonas aeruginosa
Sci Rep, 6:32822-32822, 2016

PubMed Abstract: Lipid A (also known as endotoxin) is the hydrophobic portion of lipopolysaccharides. It is an essential membrane component required for the viability of gram-negative bacteria. The enzymes involved in its biosynthesis are attractive targets for the development of novel antibiotics. LpxH catalyzes the fourth step of the lipid A biosynthesis pathway and cleaves the pyrophosphate bond of UDP-2,3-diacylglucosamine to yield 2,3-diacylglucosamine 1-phosphate (lipid X) and UMP. Here we present the structures of LpxH from Pseudomonas aeruginosa (PaLpxH). PaLpxH consists of two domains: a catalytic domain that is homologous to the metallophosphoesterases and a helical insertion domain. Lipid X was captured in the crevice between these two domains, with its phosphate group facing the dinuclear metal (Mn(2+)) center and two acyl chains buried in the hydrophobic cavity. The structures reveal that a large conformational change occurs at the lipid X binding site surface upon the binding/release of the product molecule. Based on these observations, we propose a novel model for lipid X embedding, which involves the scissor-like movement of helix α6, resulting in the release of lipid X into the lipid bilayer.

PubMed: 27609419
DOI: 10.1038/srep32822

Experimental method

X-RAY DIFFRACTION (1.96 Å)