Crystal Structure of the Quorum-Sensing Protein LuxS Reveals a Catalytic Metal Site

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 98; no. 20; pp. 11169 - 11174
• Main Authors: Hilgers, Mark T., Ludwig, Martha L.
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 25.09.2001; National Acad Sciences; The National Academy of Sciences
• Subjects: Active sites; Amidohydrolases - chemistry; Amino Acid Sequence; Atoms; Bacillus subtilis; Bacillus subtilis - enzymology; Bacteria; Bacterial Proteins - chemistry; Bacterial Proteins - metabolism; Binding Sites; Biochemistry; Biological Sciences; Carbon-Sulfur Lyases; Cloning, Molecular; Crystallography, X-Ray; Dimers; Endopeptidases - chemistry; Enzymes; Escherichia coli; Genetics; Hormones; Ligands; LuxS protein; Models, Molecular; Molecular Sequence Data; Molecules; Protein Structure, Secondary; Proteins; Recombinant Proteins - chemistry; Recombinant Proteins - metabolism; Sequence Alignment; Sequence Homology, Amino Acid; Solvents; Studies; Zinc; Zinc - metabolism
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.191223098

The ability of bacteria to regulate gene expression in response to changes in cell density is termed quorum sensing. This behavior involves the synthesis and recognition of extracellular, hormone-like compounds known as autoinducers. Here we report the structure of an autoinducer synthase, LuxS from Bacillus subtilis, at 1.6-Å resolution (Rfree= 0.204; Rwork= 0.174). LuxS is a homodimeric enzyme with a novel fold that incorporates two identical tetrahedral metal-binding sites. This metal center is composed of a Zn2+atom coordinated by two histidines, a cysteine, and a solvent molecule, and is reminiscent of active sites found in several peptidases and amidases. Although the nature of the autoinducer synthesized by LuxS cannot be deduced from the crystal structure, features of the putative active site suggest that LuxS might catalyze hydrolytic, but not proteolytic, cleavage of a small substrate. Our analysis represents a test of structure-based functional assignment.