Structure-function relationship of PE11 esterase of Mycobacterium tuberculosis with respect to its role in virulence

The lipolytic enzymes of Mycobacterium tuberculosis play a critical role in immunomodulation and virulence. Among these proteins, PE11 which also belongs to the PE/PPE family, is the smallest (∼10.8 kDa) and play a significant role in cell wall remodelling and virulence. PE11 is established to be an esterase, but its enzymatic and structural properties are not yet characterized. In this study, using homology modelling we deduced the putative structure which shows the presence of both α-helix and β-sheet structures which is in close agreement with that observed by CD spectra of the purified protein. PE11 was found to contain a Gx 3 Sx 4 G motif homologous to canonical ‘GxSxG’ motif present in many serin hydrolases. The catalytic triad appears to be located within this motif as substitution of Serine 26 and Glycine 31 residues abrogated its enzymatic activity. Gel-filtration chromatography data indicate that PE11 possibly exists as dimer and tetramer showing positive cooperativity for binding its substrates . In addition, PE11 esterase activity was found to be critical for cell wall remodelling, antibiotic resistance and conferring survival advantages to M. tuberculosis . Our data suggest that PE11 can be targeted for designing potential therapeutic strategies. • PE11 contains Gx 3 Sx 4 G motif important for its esterase activity. • Homology modelling of PE11 shows presence of both α-helix and β-sheet structures. • PE11 esterase activity is critical for cell wall remodelling and antibiotic resistance. • PE11 esterase activity is responsible for better survival of mycobacteria. • PE11 may be targeted to develop suitable therapeutics against tuberculosis.