Linked Life Data

21397998

Source:http://linkedlifedata.com/resource/pubmed/id/21397998

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2011-3-28
pubmed:databankReference
pubmed:abstractText
The enoyl-acyl carrier protein reductase of Mycobacterium tuberculosis (MTB) is a key enzyme of the type II fatty acid synthesis system. It is involved in the production of mycolic acid and is a known target for isoniazid, an effective antibiotic for tuberculosis treatment. The increasing prevalence of tuberculosis in many areas of the world, which is associated with the rise of drug-resistant MTB strains, presents a major global health threat. In this study, we attempted to identify novel antibiotics specifically targeting the MTB enoyl-acyl carrier protein reductase. We performed in silico structure-based drug screening using the crystal structure data for the MTB enoyl-acyl carrier protein reductase (PDB code; 2H7I) and a virtual compound library, which includes 152,102 chemicals. By a two-step screening method using DOCK (first screening) and GOLD (second screening), we identified 5 chemical compounds expected to have high binding affinity to the active center of the MTB enoyl-acyl carrier protein reductase. Moreover, we examined the antibiotic effects of these chemical compounds on model bacterial strains by in vitro experiments. We found that a chemical compound, which has a basic skeleton comprised of dibenzofuran, acetoamide, trizol, furyl and methylphenyl groups, completely inhibited the growth of Mycobacterium vanbaalenii and had no toxic effects on enterobacteria and cultured mammalian cells. Therefore, the chemical compound is likely to be useful in the research and development of new antibiotics for tuberculosis.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
1768-3254
pubmed:author
pubmed:copyrightInfo
Copyright © 2011 Elsevier Masson SAS. All rights reserved.
pubmed:issnType
Electronic
pubmed:volume
46
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1849-56
pubmed:meshHeading
pubmed:year
2011
pubmed:articleTitle
Identification of novel potential antibiotics for tuberculosis by in silico structure-based drug screening.
pubmed:affiliation
Department of Bioscience and Bioinformatics, Kyushu Institute of Technology, 680-4 Kawazu, Iizuka-shi, Fukuoka 820-8502, Japan.
pubmed:publicationType
Journal Article