Novel Mutations in the katG Gene in Isoniazid Resistant Mycobacterium tuberculosis Isolate

Abstract: Isoniazid (INH) resistance in Mycobacterium tuberculosis is commonly associated with mutations in katG encoding catalase-peroxidase.  A clinical isolate of M. tuberculosis L21 exhibits isoniazid resistant phenotype.  A 2.2 kb DNA fragment of katG gene from the L21 isolate had been cloned and characterized.  The L21 katG gene has four point mutations, namely T898C; G1388T; T1997C; C2035T; and one G2203 deletion.  The in silico translation analysis of the katG mutant suggests that the mutation results in a truncated protein lacking of 62 C-terminal amino acids with three amino acid substitutions, Trp300Arg, Arg463Leu, and Ile666Thr. The structural model superposition of the mutant protein with the full length protein suggests that the mutant losses an ability to form a dimer structure, and also posseses a distortion of intermolecular interactions in the substrate binding channel. 
Keywords: katG gene, KatG, MDR M. tuberculosis, Isoniazid resistance, Structure model
Author: Purkan, Ihsanawati, Debbie Soefie Retnoningrum, Yana Maolana Syah
Journal Code: jpmatematikagg130003

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