Abstract
The structures of three forms of the dimeric enzyme human inosine triphosphate pyrophosphatase (hITPA) are considered for identifying conformation changes that determine the inactivation effect of the P32T mutation. Nanosecond molecular dynamics were analyzed and the values of mean-square deviations of atoms for the wild-type and mutant homodimers, as well as the heterodimer, were calculated. Simulation of an interval of 3 ns demonstrates stronger atom displacements in mutant protomers. During the simulated time interval, the strongest changes are observed in the loop between α2 and β2 (residues 28–33, the area of the P32T mutation), the loop between β5 and β6, and the C-terminal end. The loop between α2 and β2 has two conformations characterized by different position of Phe31 side group. The distance between Cys33(Cα) and Phe31(Cz) for wild-type and mutant protomers is ~ 9.0 and 5.5 Å, respectively. These conformations are stably maintained.
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Original Russian Text © E.B. Dushanov, Kh.T. Kholmurodov, N.A. Koltovaya, 2015, published in Biofizika, 2015, Vol. 60, No. 4, pp. 646–654.
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Dushanov, E.B., Kholmurodov, K.T. & Koltovaya, N.A. Simulation of mutant P32T homo- and heterodimers of human inosine triphosphate pyrophosphatase hITPA. BIOPHYSICS 60, 529–537 (2015). https://doi.org/10.1134/S0006350915040090
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DOI: https://doi.org/10.1134/S0006350915040090