Simulating the fidelity and the three Mg mechanism of pol η and clarifying the validity of transition state theory in enzyme catalysis.

ABSTRACT: Pol η belongs to the important Y family of DNA polymerases that can catalyze translesion synthesis across sites of damaged DNA. This activity involves the reduced fidelity of Pol η for 8-oxo-7,8-dhyedro-2'-deoxoguanosin(8-oxoG). The fundamental interest in Pol η has grown recently with the demonstration of the importance of a 3rd Mg2+ ion. The current work explores both the fidelity of Pol η and the role of the 3rd metal ion, by using empirical valence bond (EVB) simulations. The simulations reproduce the observed trend in fidelity and shed a new light on the role of the 3rd metal ion. It is found that this ion does not lead to a major catalytic effect, but most probably plays an important role in reducing the product release barrier. Furthermore, it is concluded, in contrast to some impli

SUBMITTER: Yoon H 

PROVIDER: S-EPMC5531179 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature