Document Type : Original articles


1 Babylon university ,college of science

2 babylon university


Background: S. aureus can secrete enterotoxin. In this study, one non-synonymous single nucleotide polymorphism (nsSNP) that exhibits a missense impact on the enterotoxin type A protein was investigated, namely Thr136Arg.
Objective: The current investigation was carried out to predict the final consequences of this missense SNP on the enterotoxin type A protein structure, function, stability and binding affinity with antibiotics directed against this toxin.
Materials and Methods. Isolation and identification of S. aureus and genetic detection of enterotoxin A gene (sea) in this S. aureus  isolates. After sequencing the sea gene, the 3-dimensional structure of the enterotoxin type A protein was generated, and this nsSNP was highlighted in the generated 3-dimensional structure of enterotoxin type A. Several in silico tools were used to study the effect of missense SNP on this protein’s structure and function. Subsequently, a set of five in silico tools was also implemented to evaluate the effect of this SNP on the stability of enterotoxin type A upon mutation.
Results. The cumulative results of structure-function in silico tools indicated clear deleterious consequences of Thr136Arg on the protein structure and function of the enterotoxin type A protein. Further deleterious consequences of Thr136Arg were evolutionary confirmed, and the highly conserved region of the investigated SNP was validated in enterotoxin type A. In addition to structure-function predictions, all tools that utilized stability-prediction showed that this SNP exhibited a remarkable reduction in protein stability with a noticeable negative effect on the stability of enterotoxin type A. Docking experiments showed a noticeable alteration in the binding of enterotoxin type A with nafcillin, with a considerable alteration in the conformation of its 3D dimension.
Conclusion: It has been found from cumulative in silico predictions that the Thr136Arg SNP may be involved in inducing a noticeable damaging and destabilizing role on enterotoxin type A, with several consequent negative impacts on the biological activities in which this protein is involved. The binding affinity of the destabilized enterotoxin type A with the antibiotic nafcillin would be altered accordingly. This study suggests that nafcillin would bind more effectively with the Thr136Arg-damaged enterotoxin type A, which may implying that the strains having this protein may exhibit altered susceptibility to antibiotic treatment.


Main Subjects

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