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

ŠTĚPÁN, Jakub, Zora STŘELCOVÁ, Petr KULHÁNEK and Jaroslav KOČA. Reaction Mechanism of MutH Enzyme - Quantum Mechanics/Molecular Mechanics Study 2. In XV. Setkání biochemiků a molekulárních biologů. 2011. ISBN 978-80-210-5594-0.

Basic information

• Original name: Reaction Mechanism of MutH Enzyme - Quantum Mechanics/Molecular Mechanics Study 2
• Name in Czech: Reakční mechanismus enzymu MutH - Kvantově Mechanická/Molekulově mechanická studie 2
• Authors: ŠTĚPÁN, Jakub (203 Czech Republic, guarantor, belonging to the institution), Zora STŘELCOVÁ (203 Czech Republic, belonging to the institution), Petr KULHÁNEK (203 Czech Republic, belonging to the institution) and Jaroslav KOČA (203 Czech Republic, belonging to the institution).
• Edition: XV. Setkání biochemiků a molekulárních biologů, 2011.

Other information

• Original language: English
• Type of outcome: Conference abstract
• Field of Study: 10403 Physical chemistry
• Country of publisher: Czech Republic
• Confidentiality degree: is not subject to a state or trade secret
• WWW: URL
• RIV identification code: RIV/00216224:14310/11:00050263
• Organization unit: Faculty of Science
• ISBN: 978-80-210-5594-0
• Keywords (in Czech): MutH enzym QM/MM CPMD Reakční mechanismus
• Keywords in English: MutH enzyme QM/MM CPMD Reaction mechanism
• Tags: AKR, rivok

Abstract

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.

Links

• GD301/09/H004, research and development project: Name: Molekulární a strukturní biologie vybraných cytostatik. Od mechanistických studií k chemoterapii rakoviny

Investor: Czech Science Foundation

• LC06030, research and development project: Name: Biomolekulární centrum

Investor: Ministry of Education, Youth and Sports of the CR, Biomolecular centre

• MSM0021622413, plan (intention): Name: Proteiny v metabolismu a při interakci organismů s prostředím

Investor: Ministry of Education, Youth and Sports of the CR, Proteins in metabolism and interaction of organisms with the environment

• 205872, interní kód MU: Name: Program developing interdisciplinary research POtential for the STudies of BIOMolecular INteractions (Acronym: POSTBIOMIN)

Investor: European Union, Program developing interdisciplinary research POtential for the STudies of BIOMolecular INteractions, Capacities