In Silico Studies of M. Tuberculosis L-Lysine 6- Monooxygenase (Mbtg) as Potential Target and an Approach for Repurposing First Line Antitubercular Oral Drugs

Abstract

Tuberculosis deadly bacterial disease caused by Mycobacterium tuberculosis which has affected the almost all part of the world population. A exhaustive work has been done for defending this bacteria but due to emergence of resistant strain of Mycobacterium tuberculosis a search for the target and drugs to counter the bacteria is still on. In this study, we had proposed the repurposing of well known Antitubercular basic drugs against proposed target L-lysine 6-monooxygenase (mbtG) of Mycobacterium tuberculosis. L-lysine 6-monooxygenase is an essential enzyme for mycobactins formation and iron sequestration which in turn is important for the survival of the Mycobacterium. Since, the structure of L-lysine 6-monooxygenase is not solved yet, so a comparative model of the same was predicted through Modeller 9v18 using the template of Lysine monooxygenase
(NbtG )from Nocardia farcicinia (4D7E_A). The physico-chemical parameters of the predicted structure were validated using various programmes such as RAMPAGE, Procheck, Verify_3d and ProSA. We have found that Mycobacterium tuberculosis L-lysine 6- monooxygenase had similar conserved domains as present in the template (4D7E_A). Computational study was done for having an idea about the interactions between basic drugs and proposed target protein. For this we had done molecular docking using AUTODOCK4 software. For comparative analysis of result and hypothesis Flavin Adenine Dinucleotide (FAD) a natural ligand of L-lysine 6-monooxygenase was also docked with the same. Among all Antitubercular oral drugs Streptomycin showed the strongest affinity with fair molecular interactions with proposed target even stronger and better than its own natural ligand. These results depicts that streptomycin might also share the targeting to Mycobacterium tuberculosis L-lysine 6-monooxygenase (mbtG).