Detailed Information on Publication Record
2008
Second Step of Hydrolytic Dehalogenation in Haloalkane Dehalogenase Investigated by QM/MM Methods
OTYEPKA, Michal, Pavel BANÁŠ, A. MAGISTRATO, P. CARLONI, Jiří DAMBORSKÝ et. al.Basic information
Original name
Second Step of Hydrolytic Dehalogenation in Haloalkane Dehalogenase Investigated by QM/MM Methods
Name in Czech
Druhý krok hydrolytické dehalogenace v haloalkan dehalogenáze prováděný metodou QM/MM
Authors
OTYEPKA, Michal (203 Czech Republic), Pavel BANÁŠ (203 Czech Republic), A. MAGISTRATO (380 Italy), P. CARLONI (380 Italy) and Jiří DAMBORSKÝ (203 Czech Republic, guarantor)
Edition
Proteins: Structure, Function, and Bioinformatics, 2008, 0887-3585
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:
Impact factor
Impact factor: 3.419
RIV identification code
RIV/00216224:14310/08:00025615
Organization unit
Faculty of Science
UT WoS
000252836300009
Keywords in English
dehalogenase; LinB; Sphingomonas paucimobilis UT26; quantum-mechanical/molecular mechanics (QM/MM) simulations
Tags
International impact, Reviewed
Změněno: 2/7/2009 10:42, prof. Mgr. Jiří Damborský, Dr.
V originále
We investigate mechanism and energetics of the hydrolytic dehalogenation catalyzed by haloalkane dehalogenase LinB from Sphingomonas paucimobilis UT26 by Car-Parrinello (CP) and ONIOM hybrid quantum-mechanical/molecular mechanics (QM/MM) simulations, QM calculations and classical molecular dynamics. We focus on the second reaction step of the catalytic cycle, which comprises a general base-catalyzed hydrolysis of an ester intermediate to alcohol and free enzyme. In this step, a histidine residue (His272), polarized by glutamate (Glu132), acts as a base, accepting a proton from the catalytic water molecule and transferring it to an alcoholate ion. The reaction proceeds through a metastable tetrahedral intermediate, which shows an easily reversed reaction to the ester intermediate. The overall free energy barrier of the reaction calculated by potential of the mean force integration using CP-QM/MM calculations is equal to 19.5_2 kcal.mol-1. The lowering of the energy barrier of catalyzed reaction is caused by strong stabilization of the reaction intermediate and transition state by local electrostatic field of the enzyme, while its intrinsic dynamics plays a minor role. In the formation of the products, the protonated aspartic acid (Asp108) can easily adopt conformation of the relaxed state found in the free enzyme.
In Czech
V článku jsou popisovány výpočty mechanismů a energii při hydrolytické dehalogenaci katalyyované pomocí haloalkan dehalogenázou LinB z bakterie Sphingomonas paucimobilis UT26
Links
LC06010, research and development project |
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MSM0021622413, plan (intention) |
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