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

J 2007

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

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

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

10600 1.6 Biological sciences

Country of publisher

United States of America

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

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

Abstract

ORIG CZ

V originále

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.

In Czech

.....

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

Citovat

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.

@article{721208,
   author = {Negri, A. and Marco, E. and Damborský, Jiří and Gago, Frederico},
   article_number = {3},
   keywords = {Stepwise Dissection; Visualization; Catalytic Mechanism; Haloalkane Dehalogenase LinB; Molecular Dynamics Simulations; Computer Graphics},
   language = {eng},
   issn = {1093-3263},
   journal = {JOURNAL OF MOLECULAR GRAPHICS AND MODELLING},
   title = {Stepwise Dissection and Visualization of the Catalytic Mechanism of Haloalkane Dehalogenase LinB using Molecular Dynamics Simulations and Computer Graphics},
   url = {http://loschmidt.chemi.muni.cz/peg/abstracts/jmgm07.html},
   volume = {26},
   year = {2007}
}

TY  - JOUR
ID  - 721208
AU  - Negri, A. - Marco, E. - Damborský, Jiří - Gago, Frederico
PY  - 2007
TI  - Stepwise Dissection and Visualization of the Catalytic Mechanism of Haloalkane Dehalogenase LinB using Molecular Dynamics Simulations and Computer Graphics
JF  - JOURNAL OF MOLECULAR GRAPHICS AND MODELLING
VL  - 26
IS  - 3
SP  - 643-651
EP  - 643-651
SN  - 10933263
KW  - Stepwise Dissection
KW  - Visualization
KW  - Catalytic Mechanism
KW  - Haloalkane Dehalogenase LinB
KW  - Molecular Dynamics Simulations
KW  - Computer Graphics
UR  - http://loschmidt.chemi.muni.cz/peg/abstracts/jmgm07.html
N2  - 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.
ER  -

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. \textit{JOURNAL OF MOLECULAR GRAPHICS AND MODELLING}. 2007, vol.~26, No~3, p.~643-651. ISSN~1093-3263.

Detailed Information on Publication Record