Anti-Tuberculosis Potential of OJT008 against Active and Multi-Drug-Resistant Mycobacterium Tuberculosis: In Silico and In Vitro Inhibition of Methionine Aminopeptidase
Abstract
:1. Introduction
2. Results and Discussion
2.1. Cloning of MtMetAP1c and Gene Purification and Characterization of MtMetAP1c
2.2. Determination of the Catalytic Effect of the Divalent Metal of Recombinant MtMetAP1c Activity
2.3. Determination of IC50 of OJT008 for MtMetAP1c Inhibition and Minimum Inhibitory Concentrations (MICs) of OJT008 in Replicating and Multi-Drug-Resistant Mtb
2.4. Molecular Docking (In Silico) Analysis
3. Materials and Method
3.1. Materials
3.2. Method
Cloning of MtMetAP1c Gene and Expression of MtMetAP1c Protein
3.3. Determination of the Catalytic Effect of the Divalent Metal of Recombinant MtMetAP1c Activity
3.4. Determination of IC50 of OJT008 for MtMetAP1c Inhibition
3.5. Determination of Minimum Inhibitory Concentration of OJT008 in Replicating Mtb
3.6. Determination of Minimum Inhibitory Concentration of OJT008 in Multi-Drug-Resistant Mtb
3.7. Molecular Docking
MtMetAP1c Acquisition and Preparation
4. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Inhibitor | IC50 (µM) | |
---|---|---|
MtMetAP1c + 100 µM CoCl2 | MtMetAP1c + 100 µM NiCl2 | |
0JT008 | 11.81 ± 1.30 | 40.12 ± 1.12 |
Inhibitor | MIC (µg/mL) | |
---|---|---|
Replicating Mtb (CDC 1551) | Multi-Drug-Resistant Mtb (HN 3409) | |
Isoniazid | 0.25 | ND |
Kanamycin | ND | 5.00 |
0JT008 | <0.063 | <0.063 |
Co-Enzyme | ||
---|---|---|
MtMetAP1c + CoCl2 | MtMetAP1c + Ni Cl2 | |
Docking Scores (Kcal/mol) | −6.52 | −7.01 |
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Onyenaka, C.; Idowu, K.A.; Ha, N.P.; Graviss, E.A.; Olaleye, O.A. Anti-Tuberculosis Potential of OJT008 against Active and Multi-Drug-Resistant Mycobacterium Tuberculosis: In Silico and In Vitro Inhibition of Methionine Aminopeptidase. Int. J. Mol. Sci. 2023, 24, 17142. https://doi.org/10.3390/ijms242417142
Onyenaka C, Idowu KA, Ha NP, Graviss EA, Olaleye OA. Anti-Tuberculosis Potential of OJT008 against Active and Multi-Drug-Resistant Mycobacterium Tuberculosis: In Silico and In Vitro Inhibition of Methionine Aminopeptidase. International Journal of Molecular Sciences. 2023; 24(24):17142. https://doi.org/10.3390/ijms242417142
Chicago/Turabian StyleOnyenaka, Collins, Kehinde A. Idowu, Ngan P. Ha, Edward A. Graviss, and Omonike A. Olaleye. 2023. "Anti-Tuberculosis Potential of OJT008 against Active and Multi-Drug-Resistant Mycobacterium Tuberculosis: In Silico and In Vitro Inhibition of Methionine Aminopeptidase" International Journal of Molecular Sciences 24, no. 24: 17142. https://doi.org/10.3390/ijms242417142