2007 Fiscal Year Final Research Report Summary
Structural analysis for enzymatic activity of sphingomyelinase from Bacillus cereus
| Project/Area Number |
18590441
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Bacteriology (including Mycology)
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| Research Institution | Tokushima Bunri University |
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Principal Investigator |
SAKURAI J. Tokushima Bunri University, Fac. Pharm. Sci., Full Professor (80029800)
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| Co-Investigator(Kenkyū-buntansha) |
KOBAYASHI Keiko Tokushima Bunri University, Fac. Pharm. Sci., assistant Professor (90170315)
ODA M. Tokushima Bunri University, Fac. Pharm. Sci., assistant Professor (00412403)
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| Project Period (FY) |
2006 – 2007
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| Keywords | Bacillus cereus / sphingomyelinase / hemolytic activity / structural analysis / divalent cation / cleft / 3D structure / neutral SMase |
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| Research Abstract |
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.
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