Structural analysis for enzymatic activity of sphingomyelinase from Bacillus cereus

点击翻译按钮获取中文摘要

Neutral sphingomyelinase (nSMase) has been implicated in the generation of second messengers in mammalian cells. Bacillus cereus Smase (Bc-SMase) mimics the action of the endogenous mammalian nSMase in causing differentiation, development aging and apoptosis. The enzymatic activity of Bc-SMase was activated in the order of Co^<2+> > Mg^<2+> >> Ca^<2+>. The crystal structures of Bc-Smase with these metal ions were determined. The water-bridged twin divalent metal ions, Co^<2+> and Mg^<2+>, at the center of cleft were concluded to be the catalytic architecture to exert the sphingomyelinase activity. On the other hands, the architecture of Ca^<2+> binding at the site was different from that of Ca^<2+> and Mg^<2+>. The other binding site of these metal ions was at one side edge of the cleft. The crystal structure of the enzyme with Mg^<2+> or Co^<2+> at the site provides the universal structure bases for the hydrolytic activity of nSMase. In addition, the structural features and site-directed mutagenesis suggest that the specific-hairpin with the aromatic amino acid residues, the new active site, involves in binding to SM and membrane SM.