Structure - Activity Relationship of Mutant KatG from INH resistant Mycobacterium tuberculosis

• Main Authors: Purkan Purkan, Sri Puji Astuti Wahyuningsih, Wiwin Retnowati, Diah Amelia, Alfain Noerdin Alimny
• Format: Article
• Language: English
• Published: Journal of Pure and Applied Microbiology 2017-06-01
• Series: Journal of Pure and Applied Microbiology
• Subjects: katg; catalase-peroxdase; isoniazid resistance
• Online Access: https://microbiologyjournal.org/structure-activity-relationship-of-mutant-katg-frominh-resistant-mycobacterium-tuberculosis/

Mutation in katG gene of Mycobacterium tuberculosis encoding catalase-peroxidase that damage its enzyme activities is well associated with isoniazid (INH) resistance. The katG gene from INH resistant strain of M. tuberculosis clinical isolate L19 has been observed in previous study, carrying mutations of G234A and C625T, and changed the arginine residue at position 209 with cysteine in its KatG protein. However the activities of the mutant protein has been not known yet. Expression of the katG gene L19 that was done in Escherisicia coli BL21(DE3) using pCold II-DNA generated KatG protein with 80 kDa in SDS PAGE electroforegram. The mutant protein of KatG L19 decreased 43% of catalase activity and 11% of peroxidase activity against to KatG wild type (H37RV). The model structure of the mutant KatG protein had deviation structure toward KatG wt as 0,13 for number of Root Mean Square Deviations (RMSD). The mutant KatG (Arg209Cys) losed two hydrogen interactions and a van der Waals bond which present in KatG wild type. In the KatG wt protein, the both hydrogen bonds was formed between the Arg209 residu to Glu201, while the van der Waals bond occured by lingking of Arg209 residu to Glu217. Disruption in the some chemical interactions might trigger the decline in catalase-peroxidase activities of mutant KatG L19 and further it bring out the INH resistance in the clinical isolate L19.