EC Number   |
Inhibitors |
Structure  |
|---|
   1.3.1.118 | more |
SAR studies on novel inhibitor scaffolds. Inhibitor scaffolds include the diaryl ethers, pyrrolidine carboxamides, piperazine indoleformamides, pyrazoles, arylamides, fatty acids, and imidazopiperidines, all of which form ternary complexes with InhA and the NAD cofactor, as well as isoniazid and the diazaborines which covalently modify the cofactor. Analysis of the structural data has enabled the development of a common binding mode for the ternary complex inhibitors, which includes a hydrogen bond network, a large hydrophobic pocket and a third size-limited binding area comprised of both polar and non-polar groups. A critical factor in InhA inhibition involves ordering of the substrate binding loop, located close to the active site, and a direct link is proposed between loop ordering and slow onset enzyme inhibition. Slow onset inhibitors have long residence times on the enzyme target, a property that is of critical importance for in vivo activity |
 |
| 1.3.1.118 | more |
overview of 80 available crystal structures of wild-type and mutant InhA, in its apo form, in complex with its cofactor, with an analogue of its natural ligands (C16 fatty acid and/or NADH) or with inhibitors |
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| 1.3.1.118 | more |
twenty eight 2-(4-oxoquinazolin-3(4H)-yl)acetamide derivatives are synthesized and evaluated for their in vitro Mycobacterium tuberculosis InhA inhibition. Compounds are evaluated for their in vitro activity against drug sensitive and resistant Mycobacterium tuberculosis strains and cytotoxicity against RAW 264.7 cell line. Compounds are docked at the active site of InhA to understand their binding mode and differential scanning fluorimetry is performed to ascertain their protein interaction and stability |
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| 1.3.1.118 | more |
a series of piperazine derivatives is synthesized and screened as MtInhA inhibitors, which results in the identification of compounds with IC50 values in the submicromolar range |
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| 1.3.1.118 | more |
the heterologous enzyme is ectopically expressed in a yeast mutant strain from which the native gene encoding the corresponding mitochondrial FASII enzyme is missing.Using an appropriate fungal mitochondrial leader sequence, the mycobacterial protein is directed to the mitochondria, where it can rescue the respiratory growth phenotype of the mutant. The rationale behind the assay is that added antimycolates are foreseen to inhibit the mycobacterial enzyme, thereby recreating the respiratory deficiency of the original mutant, discernible as poor colony formation and growth on glycerol medium |
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| 1.3.1.118 | NAD+ |
linear competitive inhibitor versus NADH |
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| 1.3.1.118 | triclosan |
demonstration of triclosan inhibition of InhA in yeast represents a meaningful variation in studying this effect in mycobacteria, because it occurrs without the potentially confusing aspects of perturbing protein-protein interactions which are presumed vital to mycobacterial FASII, inactivating other important enzymes or eliciting a dedicated transcriptional response in Mycobacterium tuberculosis |
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| 1.3.1.118 | triclosan |
uncompetitive inhibitor |
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| 1.3.1.118 | triclosan |
- |
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| 1.3.1.118 | isoniazid |
- |
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