title: Structural basis and specificity of acyl-homoserine lactone signal production in bacterial quorum sensing.
abstract: Synthesis and detection of acyl-homoserine lactones (AHLs) enables many gram-negative bacteria to engage in quorum sensing, an intercellular signaling mechanism that activates differentiation to virulent and biofilm lifestyles. The AHL synthases catalyze acylation of S-adenosyl-L-methionine by acyl-acyl carrier protein and lactonization of the methionine moiety to give AHLs. The crystal structure of the AHL synthase, EsaI, determined at 1.8 A resolution, reveals a remarkable structural similarity to the N-acetyltransferases and defines a common phosphopantetheine binding fold as the catalytic core. Critical residues responsible for catalysis and acyl chain specificity have been identified from a modeled substrate complex and verified through functional analysis in vivo. A mechanism for the N-acylation of S-adenosyl-L-methionine by 3-oxo-hexanoyl-acyl carrier protein is proposed.
authors.affiliation: Department of Pharmacology, The University of Colorado Health Sciences Center, 4200 E. Ninth Avenue, Denver, CO 80262, USA.
authors.forename: William T
authors.initials: WT
authors.lastname: Watson
authors.forename: Timothy D
authors.initials: TD
authors.lastname: Minogue
authors.forename: Dale L
authors.initials: DL
authors.lastname: Val
authors.forename: Susanne Beck
authors.initials: SB
authors.lastname: von Bodman
authors.forename: Mair E A
authors.initials: ME
authors.lastname: Churchill
mesh_terms: D015107:4-Butyrolactone / Q000031:analogs & derivatives / Q000096:biosynthesis*; D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D001665:Binding Sites; D006090:Gram-Negative Bacteria / Q000201:enzymology* / Q000235:genetics; D008958:Models, Molecular; D008969:Molecular Sequence Data; D015394:Molecular Structure; D016297:Mutagenesis, Site-Directed; D017434:Protein Structure, Tertiary; D016415:Sequence Alignment; D015398:Signal Transduction; D013379:Substrate Specificity
chemical_list: D001426:Bacterial Proteins; C095458:EsaI protein, Erwinia stewartii; D015107:4-Butyrolactone