title: The 1.2 A structure of a novel quorum-sensing protein, Bacillus subtilis LuxS.
abstract: In bacteria, the regulation of gene expression in response to changes in cell density is called quorum sensing. The autoinducer-2 production protein LuxS, is involved in a novel quorum-sensing system and is thought to catalyse the degradation of S-ribosylhomocysteine to homocysteine and the autoinducer molecule 4,5-dihydroxy-2,3-pentadione. The crystal structure of Bacillus subtilis LuxS has been determined at 1.2 A resolution, together with the binary complexes of LuxS with S-ribosylhomocysteine and homocysteine to 2.2 and 2.3 A resolution, respectively. These structures show that LuxS is a homodimer with an apparently novel fold based on an eight-stranded 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. Access to the active site appears to be restricted and possibly requires conformational changes in the protein involving the movement of residues 125-129 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 has not been determined. The autoinducer-2 signalling pathway has been linked to aspects of bacterial virulence and pathogenicity. The structural data on LuxS will provide opportunities for targeting this enzyme for the rational design of new antibiotics.
authors.affiliation: Krebs Institute for Biomolecular Research, Department of Molecular Biology and Biotechnology, University of Sheffield, Firth Court, Western Bank, Sheffield S10 2TN, UK.
authors.forename: S N
authors.initials: SN
authors.lastname: Ruzheinikov
authors.forename: S K
authors.initials: SK
authors.lastname: Das
authors.forename: S E
authors.initials: SE
authors.lastname: Sedelnikova
authors.forename: A
authors.initials: A
authors.lastname: Hartley
authors.forename: S J
authors.initials: SJ
authors.lastname: Foster
authors.forename: M J
authors.initials: MJ
authors.lastname: Horsburgh
authors.forename: A G
authors.initials: AG
authors.lastname: Cox
authors.forename: C W
authors.initials: CW
authors.lastname: McCleod
authors.forename: A
authors.initials: A
authors.lastname: Mekhalfia
authors.forename: G M
authors.initials: GM
authors.lastname: Blackburn
authors.forename: D W
authors.initials: DW
authors.lastname: Rice
authors.forename: P J
authors.initials: PJ
authors.lastname: Baker
mesh_terms: D000595:Amino Acid Sequence; D001412:Bacillus subtilis / Q000201:enzymology*; D001426:Bacterial Proteins / Q000737:chemistry* / Q000378:metabolism*; D001665:Binding Sites; D013437:Carbon-Sulfur Lyases; D018360:Crystallography, X-Ray; D006710:Homocysteine / Q000031:analogs & derivatives / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011485:Protein Binding; D020836:Protein Structure, Quaternary; D017433:Protein Structure, Secondary; D012645:Selenomethionine / Q000378:metabolism; D016415:Sequence Alignment; D015032:Zinc / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D006710:Homocysteine; D012645:Selenomethionine; D013437:Carbon-Sulfur Lyases; C117753:LuxS protein, Bacteria; D015032:Zinc