Physical Chemistry

Theoretical model of a biochemical reaction can provide reliable chemical picture of catalytic process. Aim of this project is to model key parameters of newly proposed repair mechanism with hOGG1; the human 8-oxoG glycosylase 1. Although the crystal structure of DNA-hOGG1 complex is available since 2003, mechanism of excision of the oxidized G base remained blurring. Our previous research evidenced existence of a novel structural feature of DNA and RNA oligonucleotides - pyramidal glycosidic nitrogen (Nucleic Acids Research 37, 7321, 2009). The pyramidalization of 8-oxoG within the hOGG1 catalytic pocket allows for base excision with extremely low activation barrier that is moreover selective with respect to damaged and normal G base. The mechanism employing activation of substrate in the form of enforced pyramidalization represents new strategy within the family of base excision repair enzymes. The theoretical modeling will be conducted in collaboration with experimental laboratory of Prof. Yoshiyuki Tanaka, Tohoku University, Sendai, Japan.

Contact: vladimir.sychrovsky@uochb.cas.cz, tel. +420 220 183 234.