In silico Structural Characterization of Rv3473c from Mycobacterium tuberculosis H37Rv: Potentials in Drug Development

Abstract

Aims: Large proportion of Mycobacterium tuberculosis H37Rv proteome still needs to be characterized especially peroxidase proteins as drug targets. There is twenty (20) known peroxidases that have been annotated in the genome. Among these Rv3473c has been studied by us using suitable in silico methods. Methodology: The multiple sequence alignment of Rv3473c with PDB IDs 1BRO (277 aa), 1A7U (277 aa) and 1BRT (277 aa) indicates that the protein has well defined peroxidase motif. The 3-D molecular model of Rv3473c was generated using 1BRO, 1A7U and 1BRT as templates. Results: Structural characterization indicates that it has the ‘perhydrolase motif –G-X-S-X-G-, and the catalytic triad consists of the residues Ser73, His236 and Ser208. In addition, it has been found to contain the residues like Ser73, Phe77, Leu33, His5, Gly8, and among these Ser73 is the probable halide (bromine) binding site. Charge distribution analysis of active site indicates positively charged pocket near Ser208 of the catalytic triad whereas His236 remains within the negatively charged region. Ser73 of the ‘perhydrolase motif’ lies in the positively charged region of Rv3473c, however, another part of this motif is present in the hydrophobic region of the protein. Rv3473c uses H2O2 as nucleophile to form peracids. The presence of active site residues, oxyanion hole support the catalytic mechanism of Rv3473c as reported for other non-metal dependent bromoperoxidases. Conclusion: Rv3473c, found out to be a non-metal dependent bromoperoxidase through in silico means, may prove its efficiency in near future in designing better drugs against tuberculosis after further research on it.