The DOI matches its Crossref record; 3 of the 3 references it cites were found in a registry or an index.
Structure of the Pseudomonas aeruginosa acyl‐homoserinelactone synthase LasI
Open accessAbstract
Summary: 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.
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Cites
The Involvement of Cell-to-Cell Signals in the Development of a Bacterial Biofilm
Davies, D. G., Parsek, M. R., Pearson, J. P., Iglewski, B. H., Costerton, J. W., & Greenberg, E. P. (1998) · Science · doi:10.1126/science.280.5361.295 · Cited by 3,396
Many paths to methyltransfer: a chronicle of convergence
Schubert, H. L., Blumenthal, R. M., & Cheng, X. (2003) · Trends in Biochemical Sciences · doi:10.1016/s0968-0004(03)00090-2 · Cited by 876
Contribution of Quorum Sensing to the Virulence of Pseudomonas aeruginosa in Burn Wound Infections
Rumbaugh, K. P., Griswold, J. A., Iglewski, B. H., & Hamood, A. N. (1999) · Infection and Immunity · doi:10.1128/iai.67.11.5854-5862.1999 · Cited by 408
Cited by
Galloway, W. R. J. D., Hodgkinson, J. T., Bowden, S. D., Welch, M., & Spring, D. R. (2011) · Chemical Reviews · doi:10.1021/cr100109t · Cited by 665
Quorum sensing and bacterial biofilms
Dickschat, J. S. (2010) · Natural Product Reports · doi:10.1039/b804469b · Cited by 355
Natural history of S-adenosylmethionine-binding proteins
Kozbial, P. Z., & Mushegian, A. R. (2005) · BMC Structural Biology · doi:10.1186/1472-6807-5-19 · Cited by 297
(2023) · doi:10.1038/s41467-023-43702-4 · Cited by 55
Metadata
- Authors
- Gould, T. A., Schweizer, H. P., & Churchill, M. E. A.
- Venue
- Molecular Microbiology
- Publisher
- Wiley
- Published
- 2004-07-09
- Volume
- 53
- Issue
- 4
- Pages
- 1135-1146
- ISSN
- 0950-382X (ISSN-L)
- 1365-2958
- OpenAlex
- W1726719959
- Cited by
- 200
- References
- 3
- FWCI
- 2.41
- Type
- journal article
- Language
- en
- Open access
- bronze
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