Conformational changes allow processing of bulky substrates by a haloalkane dehalogenase with a small and buried active site

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00159816%3A_____%2F18%3A00069346" target="_blank" >RIV/00159816:_____/18:00069346 - isvavai.cz</a>

Alternative codes found

RIV/00216224:14310/18:00106486

Result on the web

<a href="http://dx.doi.org/10.1074/jbc.RA117.000328" target="_blank" >http://dx.doi.org/10.1074/jbc.RA117.000328</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1074/jbc.RA117.000328" target="_blank" >10.1074/jbc.RA117.000328</a>

Result language

angličtina

Original language name

Conformational changes allow processing of bulky substrates by a haloalkane dehalogenase with a small and buried active site

Original language description

Haloalkane dehalogenases catalyze the hydrolysis of halogen-carbon bonds in organic halogenated compounds and as such are of great utility as biocatalysts. The crystal structures of the haloalkane dehalogenase DhlA from the bacterium from Xanthobacter autotrophicus GJ10, specifically adapted for the conversion of the small 1,2-dichloroethane (DCE) molecule, display the smallest catalytic site (110 angstrom(3)) within this enzyme family. However, during a substrate-specificity screening, we noted that DhlA can catalyze the conversion of far bulkier substrates, such as the 4-(bromomethyl)-6,7-dimethoxy-coumarin (220 angstrom(3)). This large substrate cannot bind to DhlA without conformational alterations. These conformational changes have been previously inferred from kinetic analysis, but their structural basis has not been understood. Using molecular dynamic simulations, we demonstrate here the intrinsic flexibility of part of the cap domain that allows DhlA to accommodate bulky substrates. The simulations displayed two routes for transport of substrates to the active site, one of which requires the conformational change and is likely the route for bulky substrates. These results provide insights into the structure-dynamics function relationships in enzymes with deeply buried active sites. Moreover, understanding the structural basis for the molecular adaptation of DhlA to 1,2-dichloroethane introduced into the biosphere during the industrial revolution provides a valuable lesson in enzyme design by nature.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

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OECD FORD branch

10608 - Biochemistry and molecular biology

Project

Result was created during the realization of more than one project. More information in the Projects tab.

Continuities

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Publication year

2018

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Journal of Biological Chemistry

ISSN

0021-9258

e-ISSN

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Volume of the periodical

293

Issue of the periodical within the volume

29

Country of publishing house

US - UNITED STATES

Number of pages

13

Pages from-to

11505-11512

UT code for WoS article

000439449700020

EID of the result in the Scopus database

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