The 1.2 angstrom structure of a novel quorum-sensing protein, Bacillus subtilis LuxS

In bacteria, the regulation of gene expression in response to changes in ce ll density is called quorum sensing. The autoinducer-2 production protein L uxS, is involved in a novel quorum-sensing system and is thought to catalys e the degradation of S-ribosylhomocysteine to homocysteine and the autoindu cer molecule 4,5-dihydroxy-2,3-pentadione. The crystal structure of Bacillu s subtilis LuxS has been determined at 1.2 Angstrom resolution, together wi th the binary complexes of LuxS with S-ribosylhomocysteine and homocysteine to 2.2 and 2.3 Angstrom resolution, respectively. These structures show th at LuxS is a homodimer with an apparently novel fold based on an eight-stra nded beta -barrel, flanked by six alpha -helices. Each active site contains a zinc ion coordinated by the conserved residues His54, His58 and Cys126, and includes residues from both subunits. S-ribosylhomocysteine binds in a deep pocket with the ribose moiety adjacent to the enzyme-bound zinc ion. A ccess to the active site appears to be restricted and possibly requires con formational changes in the protein involving the movement of residues 125-1 29 and those at the N terminus. The structure contains an oxidised cysteine residue in the active site whose role in the biological process of LuxS ha s not been determined. The autoinducer-2 signalling pathway has been linked to aspects of bacterial virulence and pathogenicity. The structural data o n LuxS will provide opportunities for targeting this enzyme for the rationa l design of new antibiotics. (C) 2001 Academic Press.