Introducing ALZET?ew Model 2006 Pump Sign up for PNAS Online eTocs
Link: Info for AuthorsLink: Editorial BoardLink: AboutLink: SubscribeLink: AdvertiseLink: ContactLink: Sitemap Link: PNAS Home
Proceedings of the National Academy of Sciences
Link: Current Issue "" Link: Archives "" Link: Online Submission ""  Link: Advanced Search

Published online on August 8, 2005, 10.1073/pnas.0505255102

This Article
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a colleague
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My File Cabinet
Right arrow Download to citation manager
Right arrow Request Copyright Permission
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Liu, D.
Right arrow Articles by Ringe, D.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Liu, D.
Right arrow Articles by Ringe, D.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg  
What's this?

Microbiology
Three-dimensional structure of the quorum-quenching N-acyl homoserine lactone hydrolase from Bacillus thuringiensis

( bridged bimetallo center | lactonase | single-wavelength anomalous dispersion )

Dali Liu *, Bryan W. Lepore *{dagger}, Gregory A. Petsko *, Pei W. Thomas {ddagger}, Everett M. Stone {sect}, Walter Fast {ddagger}{sect}¶, and Dagmar Ringe *||

{ddagger}Division of Medicinal Chemistry, College of Pharmacy, and {sect}Graduate Program in Cell and Molecular Biology, University of Texas, Austin, TX 78712; and {dagger}Program in Bioorganic Chemistry and *Departments of Chemistry and Biochemistry and Rosenstiel Basic Medical Sciences Research Center, Brandeis University, Waltham, MA 02454-9110

Contributed by Gregory A. Petsko, June 28, 2005

The three-dimensional structure of the N-acyl-L-homoserine lactone hydrolase (AHL lactonase) from Bacillus thuringiensis has been determined, by using single-wavelength anomalous dispersion (SAD) phasing, to 1.6-Å resolution. AHLs are produced by many Gram-negative bacteria as signaling molecules used in quorum-sensing pathways that indirectly sense cell density and regulate communal behavior. Because of their importance in pathogenicity, quorum-sensing pathways have been suggested as potential targets for the development of novel therapeutics. Quorum-sensing can be disrupted by enzymes evolved to degrade these lactones, such as AHL lactonases. These enzymes are members of the metallo-{beta}-lactamase superfamily and contain two zinc ions in their active sites. The zinc ions are coordinated to a number of ligands, including a single oxygen of a bridging carboxylate and a bridging water/hydroxide ion, thought to be the nucleophile that hydrolyzes the AHLs to ring-opened products, which can no longer act as quorum signals.

Author contributions: D.L., B.W.L., P.W.T., and E.M.S. performed research; D.L., B.W.L., G.A.P., P.W.T., E.M.S., W.F., and D.R. analyzed data; G.A.P., W.F., and D.R. designed research; and D.L., B.W.L., W.F., and D.R. wrote the paper.

To whom correspondence may be addressed at: Division of Medicinal Chemistry, College of Pharmacy and the Graduate Program in Cell and Molecular Biology, University of Texas, Austin, TX 78712.

||To whom correspondence may be addressed at: Departments of Chemistry and Biochemistry and Rosenstiel Basic Medical Sciences Research Center, Brandeis University, Waltham, MA 02454-9110.

Walter Fast, E-mail: waltfast{at}mail.utexas.edu
Dagmar Ringe, E-mail: ringe{at}brandeis.edu

www.pnas.org/cgi/doi/10.1073/pnas.0505255102
Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg    What's this?


This article has been cited by other articles in HighWire Press-hosted journals:


Home page
 Microbiol. Mol. Biol. Rev.Home page
J. E. Gonzalez and N. D. Keshavan
Messing with Bacterial Quorum Sensing
Microbiol. Mol. Biol. Rev., December 1, 2006; 70(4): 859 - 875.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
G. Hagelueken, T. M. Adams, L. Wiehlmann, U. Widow, H. Kolmar, B. Tummler, D. W. Heinz, and W.-D. Schubert
The crystal structure of SdsA1, an alkylsulfatase from Pseudomonas aeruginosa, defines a third class of sulfatases
PNAS, May 16, 2006; 103(20): 7631 - 7636.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
M. H. Kim, W.-C. Choi, H. O. Kang, J. S. Lee, B. S. Kang, K.-J. Kim, Z. S. Derewenda, T.-K. Oh, C. H. Lee, and J.-K. Lee
The molecular structure and catalytic mechanism of a quorum-quenching N-acyl-L-homoserine lactone hydrolase
PNAS, December 6, 2005; 102(49): 17606 - 17611.
[Abstract] [Full Text] [PDF]