BURYŠKA, Tomáš, Lukáš DANIEL, Antonín KUNKA, Jan BREZOVSKÝ, Jiří DAMBORSKÝ and Zbyněk PROKOP. Discovery of Novel Haloalkane Dehalogenase Inhibitors. Applied and Environmental Microbiology. WASHINGTON, DC (USA): AMER SOC MICROBIOLOGY, vol. 82, No 6, p. 1958-1965. ISSN 0099-2240. doi:10.1128/AEM.03916-15. 2016.
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Basic information
Original name Discovery of Novel Haloalkane Dehalogenase Inhibitors
Authors BURYŠKA, Tomáš (203 Czech Republic, belonging to the institution), Lukáš DANIEL (203 Czech Republic, belonging to the institution), Antonín KUNKA (203 Czech Republic, belonging to the institution), Jan BREZOVSKÝ (203 Czech Republic, belonging to the institution), Jiří DAMBORSKÝ (203 Czech Republic, guarantor, belonging to the institution) and Zbyněk PROKOP (203 Czech Republic, belonging to the institution).
Edition Applied and Environmental Microbiology, WASHINGTON, DC (USA), AMER SOC MICROBIOLOGY, 2016, 0099-2240.
Other information
Original language English
Type of outcome Article in a journal
Field of Study 10600 1.6 Biological sciences
Country of publisher United States of America
Confidentiality degree is not subject to a state or trade secret
WWW URL
Impact factor Impact factor: 3.807
RIV identification code RIV/00216224:14310/16:00087944
Organization unit Faculty of Science
Doi http://dx.doi.org/10.1128/AEM.03916-15
UT WoS 000373339400032
Keywords in English SPHINGOMONAS-PAUCIMOBILIS UT26; AMBER FORCE-FIELD; MYCOBACTERIUM-TUBERCULOSIS; GENERALIZED BORN; SCORING FUNCTION; GAMMA-HEXACHLOROCYCLOHEXANE; BRADYRHIZOBIUM-JAPONICUM; CRYSTAL-STRUCTURE; PURIFICATION; SEQUENCE
Tags AKR, rivok
Changed by Changed by: Ing. Andrea Mikešková, učo 137293. Changed: 3/4/2017 12:24.
Abstract
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 toward 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 nonspecific HLD inhibitors. The second approach involved the virtual screening of 150,000 potential inhibitors against the crystal structure of an HLD from the human pathogen Mycobacterium tuberculosis H37Rv. The best inhibitor exhibited high specificity for the target structure, with an inhibition constant of 3 mu M 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.
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EE2.3.30.0037, research and development projectName: Zaměstnáním nejlepších mladých vědců k rozvoji mezinárodní spolupráce
GAP503/12/0572, research and development projectName: Konstrukce syntetické metabolické dráhy pro degradaci důležitého environmentálního polutantu proteinovým a metabolickým inženýrstvím
Investor: Czech Science Foundation
LH14027, research and development projectName: Nové koncepty a nástroje pro racionální design enzymů
Investor: Ministry of Education, Youth and Sports of the CR
LO1214, research and development projectName: Centrum pro výzkum toxických látek v prostředí (Acronym: RECETOX)
Investor: Ministry of Education, Youth and Sports of the CR
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