title: Crystal structure of the quorum-sensing protein LuxS reveals a catalytic metal site.
abstract: 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-A resolution (R(free) = 0.204; R(work) = 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 Zn(2+) 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.
authors.affiliation: Department of Biological Chemistry, University of Michigan, 930 North University Avenue, Ann Arbor, MI 48109, USA.
authors.forename: M T
authors.initials: MT
authors.lastname: Hilgers
authors.forename: M L
authors.initials: ML
authors.lastname: Ludwig
mesh_terms: D000581:Amidohydrolases / Q000737:chemistry; D000595:Amino Acid Sequence; D001412:Bacillus subtilis / Q000201:enzymology; D001426:Bacterial Proteins / Q000737:chemistry* / Q000378:metabolism*; D001665:Binding Sites; D013437:Carbon-Sulfur Lyases; D003001:Cloning, Molecular; D018360:Crystallography, X-Ray; D010450:Endopeptidases / Q000737:chemistry; D004926:Escherichia coli; D008024:Ligands; D008958:Models, Molecular; D008969:Molecular Sequence Data; D017433:Protein Structure, Secondary; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D015032:Zinc / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D008024:Ligands; D011994:Recombinant Proteins; D010450:Endopeptidases; D000581:Amidohydrolases; D013437:Carbon-Sulfur Lyases; C117753:LuxS protein, Bacteria; D015032:Zinc