BACKGROUND: Familial Mediterranean fever (FMF) is a recessively inherited disease with a variety of clinical presentations. The disease is associated with mutations in the FMF gene (MEFV), which encodes for the pyrin protein. The role of the E148Q pyrin mutation in the FMF phenotype remains inconclusive, and some authors even view it as a disease-insignificant polymorphism. The calculated change imposed by this mutation on pyrin structure may help to understand the role of this mutation. OBJECTIVES: To calculate the relative electrochemical effect of the E148Q mutation on the structure of pyrin protein. METHODS: The electronic properties of the wild-type pyrin molecule and its common mutated forms were computed for the full-length molecule and its segments, encoded by exons 2 and 10, using the HyperChem 7.5 program with one of the molecular mechanical methods (MM+). The change in the structure of the molecule, expressed as a change in energy gain, conferred by the mutations was determined. RESULTS: The E148Q mutation caused deviation from the wildtype pyrin segment encoded by exon 2 by 1.15% and from the whole pyrin molecule by 0.75%, which was comparable to the R202Q mutation and less than the M694V mutation which caused a deviation from the wild-type structure of the whole pyrin molecule by 1.5%. CONCLUSIONS: A quantum chemistry-based model suggests that the structural effect of the E148Q mutation is indeed low but not zero.
BACKGROUND:Familial Mediterranean fever (FMF) is a recessively inherited disease with a variety of clinical presentations. The disease is associated with mutations in the FMF gene (MEFV), which encodes for the pyrin protein. The role of the E148Qpyrin mutation in the FMF phenotype remains inconclusive, and some authors even view it as a disease-insignificant polymorphism. The calculated change imposed by this mutation on pyrin structure may help to understand the role of this mutation. OBJECTIVES: To calculate the relative electrochemical effect of the E148Q mutation on the structure of pyrin protein. METHODS: The electronic properties of the wild-type pyrin molecule and its common mutated forms were computed for the full-length molecule and its segments, encoded by exons 2 and 10, using the HyperChem 7.5 program with one of the molecular mechanical methods (MM+). The change in the structure of the molecule, expressed as a change in energy gain, conferred by the mutations was determined. RESULTS: The E148Q mutation caused deviation from the wildtype pyrin segment encoded by exon 2 by 1.15% and from the whole pyrin molecule by 0.75%, which was comparable to the R202Q mutation and less than the M694V mutation which caused a deviation from the wild-type structure of the whole pyrin molecule by 1.5%. CONCLUSIONS: A quantum chemistry-based model suggests that the structural effect of the E148Q mutation is indeed low but not zero.