[Structure and function of sphingomyelinase].
Bacillus cereus is one that causes of opportunistic human infections. Sphingomyelinase produced by B. cereus is assumed a virulence factor for the infection. Sphingomyelinase from Bacillus cereus (Bc-SMase) is Mg(2+)-containing metalloenzyme. Bc-SMase is a family of neutral SMase (nSMase) and mimics the actions of the endogenous mammalian nSMase in causing differentiation, development, and apoptosis. Bc-SMase may be a good model for the poorly characterized mammalian nSMase. Activation of Bc-SMase by divalent metal ions was in the order Co(2+)>Mn(2+)>Mg(2+)>>Ca(2+)>Sr(2+). Crystal structure analysis of Bc-SMase bound to Co(2+), Mg(2+), or Ca(2+) revealed that the water-bridged double divalent metal ions at the center of the cleft in both the Co(2+)- and Mg(2+)-bound forms is the catalytic architecture required for sphingomyelinase activity. In contrast, the architecture of Ca(2+) binding at the site showed only one binding site. A further single metal-binding site existed at one side edge of the cleft. Based on the highly conserved nature of amino acid residues of the binding sites, the crystal structure of Bc-SMase with Mg(2+) or Co(2+) provided a common structural framework applicable to phosphohydrolases belonging to the DNase I-like folding superfamily. In addition, our analysis provided evidence that beta-hairpin containing the aromatic amino acid residues and the metal ion of the side-edge participate in binding to sphinogmyelin and membranes containing sphingomyelin. This article summarized current knowledge of characteristics and mode of action of Bc-SMase.
Department of Microbiology, Faculty of Pharmaceutical Science, Tokushima Bunri University, Tokushima, Japan. masa@ph.bunri-u.ac.jp
Masataka
M
Oda
D001409:Bacillus cereus / Q000201:enzymology* / Q000472:pathogenicity; D002384:Catalysis; D002413:Cations, Divalent; D018360:Crystallography, X-Ray; D006868:Hydrolysis; D008670:Metals; D013108:Sphingomyelin Phosphodiesterase / Q000737:chemistry* / Q000502:physiology*; D037521:Virulence Factors
D002413:Cations, Divalent; D008670:Metals; D037521:Virulence Factors; D013108:Sphingomyelin Phosphodiesterase