1RO5

Crystal Structure of the AHL Synthase LasI

Summary for 1RO5

• Entry DOI: 10.2210/pdb1ro5/pdb
• Related: 1k4j 1kzf
• Descriptor: Autoinducer synthesis protein lasI, SULFATE ION, ZINC ION, ... (4 entities in total)
• Functional Keywords: alpha-beta-alpha sandwich, phosphopantetheine fold, signaling protein
• Biological source: Pseudomonas aeruginosa
• Total number of polymer chains: 1
• Total formula weight: 23109.91

Authors

Gould, T.A.,Schweizer, H.P.,Churchill, M.E. (deposition date: 2003-12-01, release date: 2004-08-24, Last modification date: 2024-05-22)

Primary citation

Gould, T.A.,Schweizer, H.P.,Churchill, M.E.
Structure of the Pseudomonas aeruginosa acyl-homoserinelactone synthase LasI.
Mol.Microbiol., 53:1135-1146, 2004

PubMed Abstract: The LasI/LasR quorum-sensing system plays a pivotal role in virulence gene regulation of the opportunistic human pathogen, Pseudomonas aeruginosa. Here we report the crystal structure of the acyl-homoserine lactone (AHL) synthase LasI that produces 3-oxo-C12-AHL from the substrates 3-oxo-C12-acyl-carrier protein (acyl-ACP) and S-adenosyl-L-methionine. The LasI six-stranded beta sheet platform, buttressed by three alpha helices, forms a V-shaped substrate-binding cleft that leads to a tunnel passing through the enzyme that can accommodate the acyl-chain of acyl-ACP. This tunnel places no apparent restriction on acyl-chain length, in contrast to a restrictive hydrophobic pocket seen in the AHL-synthase EsaI. Interactions of essential conserved N-terminal residues, Arg23, Phe27 and Trp33, suggest that the N-terminus forms an enclosed substrate-binding pocket for S-adenosyl-L-methionine. Analysis of AHL-synthase surface residues identified a binding site for acyl-ACP, a role that was supported by in vivo reporter assay analysis of the mutated residues, including Arg154 and Lys150. This structure and the novel explanation of AHL-synthase acyl-chain-length selectivity promise to guide the design of Pseudomonas aeruginosa-specific quorum-sensing inhibitors as antibacterial agents.

PubMed: 15306017
DOI: 10.1111/j.1365-2958.2004.04211.x

Experimental method

X-RAY DIFFRACTION (2.3 Å)