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Computational annotations of mycobacterial Rv3632 that confers its efficient function in cell wall biogenesis


Journal of Bacteriology & Mycology: Open Access
Md Amjad Beg, Sonu Chand Thakur, Fareeda Athar

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Abstract

Mycobacterium tuberculosis (Mtb), an etiological agent is a key pathogen responsible for devastating disease Tuberculosis (TB). Development of drug resistant strains and failure of BCG vaccine prompts us to develop a new therapeutic regimen. Moreover, Mtb practices a variety of machineries for avoiding its eradication by an infected host; and therefore, practical substitutions for inhibiting the host-pathogen interaction are thus required regularly. As an essential cell wall component, this manuscript updates our basic existing knowledge of Rv3632 gene, a transmembrane protein and a probable contributor of biosynthesis of the mycobacterial cell wall. The methodology used for updating the information was purely bioinformatic analysis which includes its sequence annotation, structure modelling and validation, molecular docking with already existing cell wall inhibitor and finally mutational analysis. Results showed that Rv3632 comprise of several transmembrane helices that range with different amino acid chains. Ab initio modelling was used for structure prediction which was validated by SAVES metaserver and data confirms 88.5% residues presence in the allowed region. Cell wall biosynthesis inhibitors were used to target Rv3632 due to its prediction in involved in cell wall synthesis. The docking score was as Ethionamide (-4.4), Thioacetazone (-4.4), Prothionamide (-4.3), Cycloserine (-3.7), Secnidazole (-3.4), Ethambutol (-3.4) and Metronidazole (-3.2). The study was ended by mutation analysis at TRP (W31) and TYR (Y71) and the result shows that substitution by glycine at both places decreases protein stability the most. This study enlightens the fact that mycobacterial cell wall targeting drug tolerance is majorly due to internal point mutations at specific residues. Thus, this report enhancing the understanding of molecular mechanism and components involved in mycobacterial cell wall synthesis and help in targeting those components and opens the way to novel therapeutic development.

Keywords

Rv3632, Ab initio modelling, molecular docking, point mutation, structural stability

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