Ruzheinikov S N, Das S K, Sedelnikova S E, Hartley A, Foster S J, Horsburgh M J, Cox A G, McCleod C W, Mekhalfia A, Blackburn G M, Rice D W, Baker P J
Krebs Institute for Biomolecular Research, Department of Molecular Biology and Biotechnology, University of Sheffield, Firth Court, Western Bank, Sheffield S10 2TN, UK.
J Mol Biol. 2001 Oct 12;313(1):111-22. doi: 10.1006/jmbi.2001.5027.
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.
在细菌中，响应细胞密度变化的基因表达调控被称为群体感应。自诱导物-2产生蛋白LuxS参与一种新型群体感应系统，被认为能催化S-核糖基高半胱氨酸降解为高半胱氨酸和自诱导物分子4,5-二羟基-2,3-戊二酮。枯草芽孢杆菌LuxS的晶体结构已在1.2埃分辨率下测定，LuxS与S-核糖基高半胱氨酸和高半胱氨酸的二元复合物的分辨率分别为2.2埃和2.3埃。这些结构表明，LuxS是一种同二聚体，基于一个八链β桶具有明显新颖的折叠结构，两侧有六个α螺旋。每个活性位点包含一个由保守残基His54、His58和Cys126配位的锌离子，并且包括来自两个亚基的残基。S-核糖基高半胱氨酸结合在一个深口袋中，核糖部分与酶结合的锌离子相邻。进入活性位点似乎受到限制，可能需要蛋白质发生构象变化，涉及残基125 - 129和N端残基的移动。该结构在活性位点含有一个氧化的半胱氨酸残基，其在LuxS生物学过程中的作用尚未确定。自诱导物-2信号通路与细菌毒力和致病性的多个方面有关。关于LuxS的结构数据将为以该酶为靶点进行新型抗生素的合理设计提供机会。
