Discovery of novel haloalkane dehalogenase inhibitors
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00159816%3A_____%2F16%3A00064013" target="_blank" >RIV/00159816:_____/16:00064013 - isvavai.cz</a>
Alternative codes found
RIV/00216224:14310/16:00087944
Result on the web
<a href="http://dx.doi.org/10.1128/AEM.03916-15" target="_blank" >http://dx.doi.org/10.1128/AEM.03916-15</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1128/AEM.03916-15" target="_blank" >10.1128/AEM.03916-15</a>
Alternative languages
Result language
angličtina
Original language name
Discovery of novel haloalkane dehalogenase inhibitors
Original language description
Haloalkane dehalogenases (HLDs) have recently been discovered in a number of bacteria, including symbionts and pathogens of both plants and humans. However, the biological roles of HLDs in these organisms are unclear. The development of efficient HLD inhibitors serving as molecular probes to explore their function would represent an important step towards a better understanding of these interesting enzymes. Here we report the identification of inhibitors for this enzyme family using two different approaches. The first builds on the structures of the enzymes' known substrates and led to the discovery of less potent non-specific HLD inhibitors. The second approach involved the virtual screening of 150,000 potential inhibitors against the crystal structure of a HLD from the human pathogen Mycobacterium tuberculosis H37Rv. The best inhibitor exhibited high specificity for the target structure, with an inhibition constant of 3 μM and a molecular architecture that clearly differs from those of all known HLD substrates. The new inhibitors will be used to study the natural functions of HLDs in bacteria, to probe their mechanisms, and to achieve their stabilization.
Czech name
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Czech description
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Classification
Type
J<sub>x</sub> - Unclassified - Peer-reviewed scientific article (Jimp, Jsc and Jost)
CEP classification
EE - Microbiology, virology
OECD FORD branch
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Result continuities
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)
Others
Publication year
2016
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Applied and Environmental Microbiology
ISSN
0099-2240
e-ISSN
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Volume of the periodical
82
Issue of the periodical within the volume
6
Country of publishing house
US - UNITED STATES
Number of pages
8
Pages from-to
1958-1965
UT code for WoS article
000373339400032
EID of the result in the Scopus database
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