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.
Arylamide inhibitors and a substrate are positioned at the same site which indicates the competitive inhibitor function of arylamides.
Based on our findings, the amide carbonyl oxygen causes the selectivity of arylamide inhibitors for Inh A inhibition.
An important element in gaining control of this epidemic is developing an understanding of the molecular basis of resistance to the most important antituberculosis drugs: isoniazid, rifampin, and pyrazinamide.
On the basis of this information, more exacting laboratory testing, and ultimately more appropriate and timely treatment regimens, can be developed.
Results show that isonicotinic acyl-NADH (INADH) has an extremely high binding affinity toward the wild type Inh A by forming stronger interactions compared to the parent drug (isoniazid) (INH).
Due to the increase of hydrophobicity and reduction in the side chain's volume of A94 of mutant type Inh A, both INADH and the mutated protein become more mobile.
Less common is cross-resistance, in which resistance occurs between drugs that are chemically related and/or have a similar target within the mycobacterial cell (ie rifampin and other rifamycin derivatives, or isoniazid and ethionamide) [ is not always clear.Moreover, this moiety is crucial for the affinity of the arylamide–Inh A interactions with Tyr158 and NADH to form hydrogen bonds.It is possible to enhance the selectivity of arylamide inhibitors to reach the Inh A target by introducing a hydrophilic substituent into the aryl ring A.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.