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PresentationsAnalysis of the P32T substitution effect to interaction between protomers of human inosine triphosphat pirophosphogidrolase hITPAJoint Institute for Nuclear Research, Laboratory of Radiation Biology, 141980, Dubna, Joliot Curie str. 6 Moscow region Russia, koltovaya@jinr.ru The enzyme inosine triphosphate pirophosphogidrolase (ITPA, Inosine Triphosphate PyrophosphatAse) supports a balance of nucleotides [1]. The polymorphism of hITPA is known. The most significant decrease in enzyme activity was observed in the polymorphic form of R32T-hITPA. This form of enzyme causes a genetic instability of microorganisms and modifies the sensitivity to certain drugs in human organism. For identify conformational changes of inosine phosphatase caused by R32T-substitution used structure (PDB entry 2J4E) of 2.8 Å-resolution as template [2]. The value of the mean square deviation of the atoms (RMSD) is calculated for the wild-homodimers of wild type (P32/P32) and mutant (T32/T32) and symmetrical mutant heterodimers (P32/T32 and T32/P32). It is shown that the RMSD for protomers is lower than for dimers. Identified areas that key contributed to the overall change for the conformation of the enzyme. Particular attention was paid to hydrogen bonds, determining the interaction between the protomers. It is shown that the R32T-substitution induces the weakening of hydrogen bonds between the protomers.
References. 1. Simone PD, Struble LR, Kellezi A, et al., The human ITPA polymorphic variant P32T is destabilized by the unpacking of the hydrophobic core // J. Struct. Biol. 2013.182:197-208. 2. Stenmark P, Kursula P, Flodin S, et al., Crystal structure of human inosine triphosphatase. Substitute binding and implication of the inosine triphosphatase deficiency mutation P32T // J. Biol. Chem. 2007. 282: 3182-3187.
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