Biological characterization of the zinc site coordinating histidine residues of staphylococcal enterotoxin C2.
The bacterial toxin staphylococcal enterotoxin C2 (SEC2) can cause staphylococcal toxic shock syndrome and food poisoning. Although the previously determined crystal structure of SEC2 revealed that some histidine residues (His47, His118 and His122) contribute to the binding of zinc ions, little is known about their biological roles in SEC2. This prompted us to investigate the role of the zinc site coordinating histidine residues in the biological activities of SEC2. The mutants with substitutions at positions 118 and 122 all retained T-cell stimulatory activity, whereas the histidine mutants at position 47 were defective in the ability to stimulate T-cell proliferation. Further toxicity assays in vivo indicated that mutants SEC2-H118A and SEC2-H122A were defective in emetic and febrile activities. However, mutant SEC2-H47A could cause significant emetic and febrile responses in comparison with the other two histidine mutants. These findings suggested that the zinc-coordinating histidine residues play significant roles in superantigen and toxic activities of SEC2 and further implied that superantigen and febrile activities could be separable in staphylococcal enterotoxins. The results also show that it should be possible to design new SEC2 immunotherapeutic agents that have superantigen activity and low toxicity.
Wang
Xiaogang
X
Graduate University of the Chinese Academy of Sciences, Beijing 100039, PR China.|Institute of Applied Ecology, Chinese Academy of Sciences, Shenyang 110016, PR China.
Zhang
Huiwen
H
Institute of Applied Ecology, Chinese Academy of Sciences, Shenyang 110016, PR China.
Xu
Mingkai
M
Institute of Applied Ecology, Chinese Academy of Sciences, Shenyang 110016, PR China.
Cai
Yongming
Y
Tianjin Institute of Pharmaceutical Research, Tianjin 300193, PR China.
Liu
Changxiao
C
Tianjin Institute of Pharmaceutical Research, Tianjin 300193, PR China.
Su
Zhencheng
Z
Institute of Applied Ecology, Chinese Academy of Sciences, Shenyang 110016, PR China.
Zhang
Chenggang
C
Institute of Applied Ecology, Chinese Academy of Sciences, Shenyang 110016, PR China.
D019943:Amino Acid Substitution; D000818:Animals; D001665:Binding Sites; D002415:Cats; D045744:Cell Line, Tumor; D004768:Enterotoxins / Q000276:immunology / Q000378:metabolism*; D005260:Female; D006639:Histidine / Q000737:chemistry*; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D016297:Mutagenesis, Site-Directed; D011749:Pyrogens / Q000276:immunology / Q000378:metabolism; D011817:Rabbits; D013211:Staphylococcus aureus / Q000276:immunology / Q000378:metabolism*; D018089:Superantigens / Q000276:immunology / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology; D015032:Zinc / Q000737:chemistry*
D004768:Enterotoxins; D011749:Pyrogens; D018089:Superantigens; C034959:enterotoxin C, staphylococcal; D006639:Histidine; D015032:Zinc