Publication details

Reaction Mechanism of MutH Enzyme - Quantum Mechanics/Molecular Mechanics Study 2

Authors

ŠTĚPÁN Jakub STŘELCOVÁ Zora KULHÁNEK Petr KOČA Jaroslav

Year of publication 2011
Type Conference abstract
MU Faculty or unit

Faculty of Science

Citation
Description Knowledge of enzymes reaction mechanisms can be helpful in many fields such as biology, medicine or pharmacy. In our study, we are focused on MutH enzyme, which is an integral part of Methyl-directed Mismatch Repair together with MutL and MutS enzymes. A mismatch introduced during DNA replication is recognized by MutS enzyme, information about the mismatch is transferred through MutL to MutH enzyme. MutH specifically recognizes the GATC sequence on daughter DNA strand and cleaves this strand close to the G base. Wrong paired base is removed and after that the correct base pairing is reestablished [1]. Main goal of our project is the understanding of the reaction mechanism of MutH enzyme. We present the Quantum Mechanics / Molecular Mechanics (QM/MM) study of the MutH enzyme reactivity based on models prepared from the available crystal structures of protein / DNA complex [2]. The cleavage mechanism is studied on ab-initio level using CPMD implementation of Density Functional Theory. We are considering two possible nucleophiles (H2O and OH-). We are comparing two different models of the protein / DNA complexes with both: inhibitor (Ca2+ ions) and activator (Mg2+ ions) of the cleavage reaction. We evaluate free energy profiles of various processes in active site including cleveage itself, such data give us insight to reaction mechanism pathway.
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