Stepwise Dissection and Visualization of the Catalytic Mechanism of Haloalkane Dehalogenase LinB using Molecular Dynamics Simulations and Computer Graphics

NEGRI, A., E. MARCO, Jiří DAMBORSKÝ and Frederico GAGO. Stepwise Dissection and Visualization of the Catalytic Mechanism of Haloalkane Dehalogenase LinB using Molecular Dynamics Simulations and Computer Graphics. JOURNAL OF MOLECULAR GRAPHICS AND MODELLING. 2007, vol. 26, No 3, p. 643-651. ISSN 1093-3263.

Basic information

• Original name: Stepwise Dissection and Visualization of the Catalytic Mechanism of Haloalkane Dehalogenase LinB using Molecular Dynamics Simulations and Computer Graphics
• Name in Czech: Kroková analyza a a visualizace katalytického mechanismu haloalkan dehalogenáz LinB použitím molekularně-dynamické simulace.
• Authors: NEGRI, A. (724 Spain), E. MARCO (724 Spain), Jiří DAMBORSKÝ (203 Czech Republic, guarantor) and Frederico GAGO (724 Spain).
• Edition: JOURNAL OF MOLECULAR GRAPHICS AND MODELLING, 2007, 1093-3263.

Other information

• Original language: English
• Type of outcome: Article in a journal
• Field of Study: 10600 1.6 Biological sciences
• Country of publisher: United States of America
• Confidentiality degree: is not subject to a state or trade secret
• WWW: URL
• Impact factor: Impact factor: 1.932
• RIV identification code: RIV/00216224:14310/07:00022385
• Organization unit: Faculty of Science
• UT WoS: 000250622300008
• Keywords in English: Stepwise Dissection; Visualization; Catalytic Mechanism; Haloalkane Dehalogenase LinB; Molecular Dynamics Simulations; Computer Graphics
• Tags: CATALYTIC MECHANISM, computer graphics, haloalkane dehalogenase LinB, molecular dynamics simulations, Stepwise Dissection, visualization
• Tags: International impact, Reviewed

Abstract

The different steps of the dehalogenation reaction carried out by LinB on three different substrates have been characterized using a combination of quantum mechanical calculations and molecular dynamics simulations. This has allowed us to obtain information in atomic detail about each step of the reaction mechanism, that is, substrate entrance and achievement of the near-attack conformation, transition state stabilization within the active site, halide stabilization, water molecule activation and subsequent hydrolytic attack on the ester intermediate with formation of alcohol, and finally product release. Importantly, no bias or external forces were applied during the whole procedure so that both intermediates and products were completely free to sample configuration space in order to adapt to the plasticity of the active site and/or search for an exit. Differences in substrate reactivity were found to be correlated with the ease of adopting the near-attack conformation and two different exit pathways were found for product release that do not interfere with substrate entrance. Additional support for the different entry and exit pathways was independently obtained from an examination of the enzyme's normal modes.

Abstract (in Czech)

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Links

• 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