The results support the assumption that the conversion of prodrug isoniazid into its active form INADH is me Pour bénéficier de nos services (strictement destinés aux membres de la communauté CNRS (Centre National de la Recherche Scientifique), de l'ESR français (Enseignement Supérieur et Recherche), et du secteur public français & étranger) : - Export vers Endnote, Procite, Reference Manager...(au format RIS)- Export au format Bib Te X- Export au format txt- Export vers Zotero (cliquez sur l'icone zotero affichée en barre d'adresse pour importer dans zotero)- Export vers Mendeley (importez dans mendeley via le Web Importer -cf continuing rise in tuberculosis incidence and the problem of drug resistance strains have prompted the research on new drug candidates and the mechanism of drug resistance.from patients without a history of previous treatment should be referred to as 'drug resistance among new cases' (instead of 'primary resistance').Isolation of a drug-resistant strain from patients who have been treated for tuberculosis for at least 1 month should be referred to as 'drug resistance among previously treated patients' (instead of 'acquired resistance').The continuing rise in tuberculosis incidence and the problem of drug resistance strains have prompted the research on new drug candidates and the mechanism of drug resistance.Molecular docking and molecular dynamics simulation (MD) were performed to study the binding of isoniazid onto the active site of Mycobacterium tuberculosis enoyl-acyl carrier protein reductase (Inh A) in an attempt to address the mycobacterial resistance against isoniazid.
However, the reduced interaction caused by the fluctuation of INADH and the mutant protein only inflected minor resistance in the mutant strain as inferred from free energy calculation.
The results support the assumption that the conversion of prodrug isoniazid into its active form INADH is mediated by Kat G as a necessary step prior to target binding on Inh A.
Our findings also contribute to a better understanding of INH resistance in mutant type.
to antimycobacterial drugs is the consequence of spontaneous mutations in genes that encode either the target of the drug, or enzymes that are involved in drug activation.
Resistance-associated point mutations, deletions, or insertions have been described for all first-line drugs (isoniazid, rifampin, pyrazinamide, ethambutol, and streptomycin), and for several second-line and newer drugs (ethionamide, fluoroquinolones, macrolides, nitroimidazopyrans) .]]