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Statements

Subject Item
n2:RIV%2F00216224%3A14310%2F12%3A00057142%21RIV13-AV0-14310___
rdf:type
n10:Vysledek skos:Concept
dcterms:description
Many enzymes have buried active sites. The properties of the tunnels connecting the active site with bulk solvent affect ligand binding and unbinding and also the catalytic properties. Here, we investigate ligand passage in the haloalkane dehalogenase enzyme LinB and the effect of replacing leucine by a bulky tryptophan at a tunnel-lining position. Transient kinetic experiments show that the mutation significantly slows down the rate of product release. Moreover, the mechanism of bromide ion release is changed from a one-step process in the wild type enzyme to a two-step process in the mutant. The rate constant of bromide ion release corresponds to the overall steady-state turnover rate constant, suggesting that product release became the rate-limiting step of catalysis in the mutant. We explain the experimental findings by investigating the molecular details of the process computationally. Many enzymes have buried active sites. The properties of the tunnels connecting the active site with bulk solvent affect ligand binding and unbinding and also the catalytic properties. Here, we investigate ligand passage in the haloalkane dehalogenase enzyme LinB and the effect of replacing leucine by a bulky tryptophan at a tunnel-lining position. Transient kinetic experiments show that the mutation significantly slows down the rate of product release. Moreover, the mechanism of bromide ion release is changed from a one-step process in the wild type enzyme to a two-step process in the mutant. The rate constant of bromide ion release corresponds to the overall steady-state turnover rate constant, suggesting that product release became the rate-limiting step of catalysis in the mutant. We explain the experimental findings by investigating the molecular details of the process computationally.
dcterms:title
A Single Mutation in a Tunnel to the Active Site Changes the Mechanism and Kinetics of Product Release in Haloalkane Dehalogenase LinB A Single Mutation in a Tunnel to the Active Site Changes the Mechanism and Kinetics of Product Release in Haloalkane Dehalogenase LinB
skos:prefLabel
A Single Mutation in a Tunnel to the Active Site Changes the Mechanism and Kinetics of Product Release in Haloalkane Dehalogenase LinB A Single Mutation in a Tunnel to the Active Site Changes the Mechanism and Kinetics of Product Release in Haloalkane Dehalogenase LinB
skos:notation
RIV/00216224:14310/12:00057142!RIV13-AV0-14310___
n10:predkladatel
n13:orjk%3A14310
n3:aktivita
n17:P
n3:aktivity
P(ED0001/01/01), P(IAA401630901)
n3:cisloPeriodika
34
n3:dodaniDat
n19:2013
n3:domaciTvurceVysledku
n9:3599019 n9:1030175 Góra, Artur Wiktor n9:4187911
n3:druhVysledku
n14:J
n3:duvernostUdaju
n20:S
n3:entitaPredkladatele
n16:predkladatel
n3:idSjednocenehoVysledku
120620
n3:idVysledku
RIV/00216224:14310/12:00057142
n3:jazykVysledku
n15:eng
n3:klicovaSlova
HLD; haloalkane dehalogenase; MD; molecular dynamics; RAMD; random acceleration molecular dynamics; ABF; adaptive biasing force; RC; reaction coordinate; FEP; free energy perturbation; NATA; N-acetyltryptophan amide
n3:klicoveSlovo
n7:NATA n7:RAMD n7:HLD n7:haloalkane%20dehalogenase n7:N-acetyltryptophan%20amide n7:RC n7:ABF n7:FEP n7:adaptive%20biasing%20force n7:reaction%20coordinate n7:free%20energy%20perturbation n7:MD n7:random%20acceleration%20molecular%20dynamics n7:molecular%20dynamics
n3:kodStatuVydavatele
US - Spojené státy americké
n3:kontrolniKodProRIV
[1CC491546B0D]
n3:nazevZdroje
The Journal of Biological Chemistry
n3:obor
n18:EB
n3:pocetDomacichTvurcuVysledku
4
n3:pocetTvurcuVysledku
7
n3:projekt
n8:ED0001%2F01%2F01 n8:IAA401630901
n3:rokUplatneniVysledku
n19:2012
n3:svazekPeriodika
287
n3:tvurceVysledku
Biedermannová, Lada Damborský, Jiří Góra, Artur Wiktor Kovács, Mihály Prokop, Zbyněk Wade, Rebecca C. Šebestová, Eva
n3:wos
000308074600073
s:issn
0021-9258
s:numberOfPages
13
n11:doi
10.1074/jbc.M112.377853
n6:organizacniJednotka
14310