Structure and biological activities of beta toxin from Staphylococcus aureus.
Beta toxin is a neutral sphingomyelinase secreted by certain strains of Staphylococcus aureus. This virulence factor lyses erythrocytes in order to evade the host immune system as well as scavenge nutrients. The structure of beta toxin was determined at 2.4-A resolution using crystals that were merohedrally twinned. This structure is similar to that of the sphingomyelinases of Listeria ivanovii and Bacillus cereus. Beta toxin belongs to the DNase I folding superfamily; in addition to sphingomyelinases, the proteins most structurally related to beta toxin include human endonuclease HAP1, Escherichia coli endonuclease III, bovine pancreatic DNase I, and the endonuclease domain of TRAS1 from Bombyx mori. Our biological assays demonstrated for the first time that beta toxin kills proliferating human lymphocytes. Structure-directed active site mutations show that biological activities, including hemolysis and lymphotoxicity, are due to the sphingomyelinase activity of the enzyme.
Huseby
Medora
M
Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, Minnesota, USA.
Shi
Ke
K
Brown
C Kent
CK
Digre
Jeff
J
Mengistu
Fikre
F
Seo
Keun Seok
KS
Bohach
Gregory A
GA
Schlievert
Patrick M
PM
Ohlendorf
Douglas H
DH
Earhart
Cathleen A
CA
D000595:Amino Acid Sequence; D001427:Bacterial Toxins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D001665:Binding Sites; D049109:Cell Proliferation / Q000187:drug effects / Q000528:radiation effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D006460:Hemolysin Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D008214:Lymphocytes / Q000187:drug effects; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D013108:Sphingomyelin Phosphodiesterase / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D013211:Staphylococcus aureus / Q000737:chemistry* / Q000235:genetics
D001427:Bacterial Toxins; D006460:Hemolysin Proteins; D013108:Sphingomyelin Phosphodiesterase; C029878:hlb protein, Staphylococcus aureus