2DDR

Crystal structure of sphingomyelinase from Bacillus cereus with calcium ion

Summary for 2DDR

• Entry DOI: 10.2210/pdb2ddr/pdb
• Related: 2DDS 2DDT
• Descriptor: Sphingomyelin phosphodiesterase, CALCIUM ION (3 entities in total)
• Functional Keywords: dnase i like folding, riken structural genomics/proteomics initiative, rsgi, structural genomics, hydrolase
• Biological source: Bacillus cereus
• Cellular location: Secreted: P11889
• Total number of polymer chains: 4
• Total formula weight: 137692.64

Authors

Ago, H.,Oda, M.,Takahashi, M.,Tsuge, H.,Ochi, S.,Katunuma, N.,Miyano, M.,Sakurai, J.,RIKEN Structural Genomics/Proteomics Initiative (RSGI) (deposition date: 2006-02-02, release date: 2006-05-02, Last modification date: 2011-07-13)

Primary citation

Ago, H.,Oda, M.,Takahashi, M.,Tsuge, H.,Ochi, S.,Katunuma, N.,Miyano, M.,Sakurai, J.
Structural Basis of the Sphingomyelin Phosphodiesterase Activity in Neutral Sphingomyelinase from Bacillus cereus.
J.Biol.Chem., 281:16157-16167, 2006

PubMed Abstract: Sphingomyelinase (SMase) from Bacillus cereus (Bc-SMase) hydrolyzes sphingomyelin to phosphocholine and ceramide in a divalent metal ion-dependent manner. Bc-SMase is a homologue of mammalian neutral SMase (nSMase) and mimics the actions of the endogenous mammalian nSMase in causing differentiation, development, aging, and apoptosis. Thus Bc-SMase may be a good model for the poorly characterized mammalian nSMase. The metal ion activation of sphingomyelinase activity of Bc-SMase was in the order Co2+ > or = Mn2+ > or = Mg2+ >> Ca2+ > or = Sr2+. The first crystal structures of Bc-SMase bound to Co2+, Mg2+, or Ca2+ were determined. The water-bridged double divalent metal ions at the center of the cleft in both the Co2+- and Mg2+-bound forms were concluded to be the catalytic architecture required for sphingomyelinase activity. In contrast, the architecture of Ca2+ binding at the site showed only one binding site. A further single metal-binding site exists at one side edge of the cleft. Based on the highly conserved nature of the residues of the binding sites, the crystal structure of Bc-SMase with bound Mg2+ or Co2+ may provide a common structural framework applicable to phosphohydrolases belonging to the DNase I-like folding superfamily. In addition, the structural features and site-directed mutagenesis suggest that the specific beta-hairpin with the aromatic amino acid residues participates in binding to the membrane-bound sphingomyelin substrate.

PubMed: 16595670
DOI: 10.1074/jbc.M601089200

Experimental method

X-RAY DIFFRACTION (1.4 Å)