Structural Basis and Specificity of Acyl-Homoserine Lactone Signal Production in Bacterial Quorum Sensing

• Published in: Molecular cell 2002-03, Vol.9 (3), p.685-694
• Main Authors: Watson, William T., Minogue, Timothy D., Val, Dale L., von Bodman, Susanne Beck, Churchill, Mair E.A.
• Format: Article
• Language: English
• Subjects: 4-Butyrolactone - analogs & derivatives; 4-Butyrolactone - biosynthesis; Amino Acid Sequence; Bacterial Proteins - chemistry; Bacterial Proteins - genetics; Bacterial Proteins - metabolism; Binding Sites; Gram-Negative Bacteria - enzymology; Gram-Negative Bacteria - genetics; Models, Molecular; Molecular Sequence Data; Molecular Structure; Mutagenesis, Site-Directed; Protein Structure, Tertiary; Sequence Alignment; Signal Transduction; Substrate Specificity
• ISSN: 1097-2765; 1097-4164
• DOI: 10.1016/S1097-2765(02)00480-X

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 Å 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.