Crystal structure of the quorum-sensing protein LuxS reveals a catalytic metal site

The ability of bacteria to regulate gene expression in response to changes in cell density is termed quorum sensing. This behavior involves the synthe sis and recognition of extracellular, hormonelike compounds known as autoin ducers. Here we report the structure of an autoinducer synthase, LuxS from Bacillus subtilis, at 1.6-Angstrom resolution (R-free = 0.204; R-work = 0.1 74). LuxS is a homodimeric enzyme with a novel fold that incorporates two i dentical tetrahedral metal-binding sites. This metal center is composed of a Zn2+ atom coordinated by two histidines, a cysteine, and a solvent molecu le, and is reminiscent of active sites found in several peptidases and amid ases. Although the nature of the autoinducer synthesized by LuxS cannot be deduced from the crystal structure, features of the putative active site su ggest that LuxS might catalyze hydrolytic, but not proteolytic, cleavage of a small substrate. Our analysis represents a test of structure-based funct ional assignment.