Novel mutations in <Emphasis Type="Italic">katG</Emphasis> gene of a clinical isolate of isoniazid-resistant <Emphasis Type="Italic">Mycobacterium tuberculosis</Emphasis> |
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Authors: | Purkan Ihsanawati Yana M Syah Debbie S Retnoningrum Achmad S Noer Shigeru Shigeoka Dessy Natalia |
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Institution: | 1.Biochemistry Research Division, Faculty of Mathematics and Natural Sciences,Bandung Institute of Technology,Bandung,Indonesia;2.Chemistry Department, Faculty of Sciences and Technology,Airlangga University,Surabaya,Indonesia;3.School of Pharmacy,Bandung Institute of Technology,Bandung,Indonesia;4.Plant Molecular Physiology Lab, Department of Advance Bioscience,Kinki University,Nakamachi, Nara,Japan |
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Abstract: | Most of isoniazid-resistant Mycobacterium tuberculosis evolved due to mutation in the katG gene encoding catalase-peroxidase. A set of new mutations, namely T1310C, G1388T, G1481A, T1553C, and A1660G, which correspond
to amino acid substitutions of L437P, R463L, G494D, I518T, and K554E, in the katG gene of the L10 clinical isolate M. tuberculosis was identified. The wild-type and mutant KatG proteins were expressed in Escherichia coli BL21(DE3) as a protein of 80 kDa based on sodium dodecyl sulphate-polyacrylamide gel electrophoresis analysis. The mutant
KatG protein exhibited catalase and peroxidase activities of 4.6% and 24.8% toward its wild type, respectively, and retained
19.4% isoniazid oxidation activity. The structure modelling study revealed that these C-terminal mutations might have induced
formation of a new turn, perturbing the active site environment and also generated new intramolecular interactions, which
could be unfavourable for the enzyme activities. |
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