Effect of single amino acid mutations on function of Mycobacterium tuberculosis H37RV and H37RA by computational...

Studies have been reported on genomic analysis to explain virulence of MTB H37Rv vs. MTB H37Ra strain. Proteomic comparison analysis at our centre has shown variability of 244 proteins in MTB H37Rv. A single amino acid mutation in protein sequence may cause alteration in protein structure and function that may account for virulence and drug resistance properties of pathogenic organisms.

To find the effect of single amino acid mutations on Mycobacterium tuberculosis H37Rv and H37Ra using computational approaches

Proteins with single amino acid mutation were analysed by different mutation analysis systems such as SIFT, PolyPhen, PROVEAN and HOPE. Subsequently, structure comparison of proposed modelled structure of mutant proteins of MTB H37Ra with native proteins of MTB H37Rv was performed.

We observed that amongst 40 single amino acid mutated proteins of MTB H37Ra, five were found to be damaged by all the mutation analysis systems. Upon structure comparison, the RMSD values between the native and mutant type proteins were found to be significantly higher. All the five proteins showed important biological function in MTB H37Rv. Further, when these five proteins of MTB H37Ra were compared with corresponding proteins of other virulent strains of MTB (i.e. F11 and CDC 1551), similar observation was made.

The data suggests the important role of single amino acid mutation in five proteins in causing changes in the virulence and pathogenicity of clinical strains of MTB.