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Mutation of katG in a clinical isolate of Mycobacterium tuberculosis: effects on catalase-peroxidase for isoniazid activation.
| Content Provider | Semantic Scholar |
|---|---|
| Author | Purkan Ihsanawati Natalia, Dessy Syah, Yana M. Retnoningrum, Debbie Sofie Kusuma, Heri Septya |
| Copyright Year | 2016 |
| Abstract | Mutations in katG gene are often associated with isoniazid (INH) resistance in Mycobacterium tuberculosis strain. This research was perfomed to identify the katG mutation in clinical isolate (L8) that is resistant to INH at 1 μg/ml. In addition to characterize the catalase-peroxidase of KatG L8 and perform the ab initio structural study of the protein to get a more complete understanding in drug activation and the resistance mechanism. The katG gene was cloned and expressed in Escherichia coli, then followed by characterization of catalase-peroxidase of KatG. The structure modelling was performed to know a basis of alterations in enzyme activity. A substitution of A713G that correspond to Asn238Ser replacement was found in the L8 katG. The Asn238Ser modification leads to a decline in the activity of catalase-peroxidase and INH oxidation of the L8 KatG protein. The catalytic efficiency (Kcat/KM) of mutant KatGAsn238Ser respectively decreases to 41 and 52% for catalase and peroxidase. The mutant KatGAsn238Ser also shows a decrease of 62% in INH oxidation if compared to a wild type KatG (KatGwt). The mutant Asn238Ser might cause instability in the substrate binding site of KatG, because of removal of a salt bridge connecting the amine group of Asn238 to the carboxyl group of Glu233, which presents in KatGwt. The lost of the salt bridge in the substrate binding site in mutant KatGAsn238Ser created changes unfavorable for enzyme activities, which in turn emerge as INH resistance in the L8 isolate of M. tuberculosis. |
| Starting Page | 71 |
| Ending Page | 81 |
| Page Count | 11 |
| File Format | PDF HTM / HTML |
| DOI | 10.15407/ubj88.05.071 |
| PubMed reference number | 29235814 |
| Journal | Medline |
| Volume Number | 88 |
| Issue Number | 5 |
| Alternate Webpage(s) | http://ukrbiochemjournal.org/wp-content/uploads/2016/11/Purkan_5_16.pdf |
| Alternate Webpage(s) | https://doi.org/10.15407/ubj88.05.071 |
| Journal | Ukrainian biochemical journal |
| Language | English |
| Access Restriction | Open |
| Content Type | Text |
| Resource Type | Article |
