MptpB, a virulence factor from Mycobacterium tuberculosis, exhibits triple-specificity phosphatase activity

Nicola Beresford , Sumayya Patel , Jane Armstrong , Balázs Szöor , Anthony P Fordham-Skelton , Lydia Tabernero (1)

1 Life Sciences

Bacterial pathogens have developed sophisticated mechanisms of evading the immune system to survive in the infected host cells. Central to pathogenesis of Mycobacterium tuberculosis is the arrest of phagosome maturation partly through interference with phosphatidylinositol signalling. The protein phosphatase MptpB is an essential secreted virulence factor in M. tuberculosis. A combination of bioinformatics analysis, enzyme kinetics and substrate specificity characterization revealed that MptpB exhibits both dual-specificity protein phosphatase activity and, importantly, phosphoinositide phosphatase activity. Mutagenesis of conserved residues in the active site signature indicates a cysteine-based mechanism of dephosphorylation and identifies two new catalytic residues, Asp165, essential in catalysis and Lys164, apparently involved in substrate specificity. Sequence similarities with mammalian lipid phosphatases and preference for phosphoinositide substrates, suggests a potential novel role of MptpB in phosphatidylinositol metabolism in the host and opens new perspectives for the role of this phosphatase in mycobacteria pathogenicity.

Mots clés: Life Sciences

Nicola Beresford, Sumayya Patel, Jane Armstrong, Balázs Szöor, Anthony P Fordham-Skelton, et al.. MptpB, a virulence factor from Mycobacterium tuberculosis, exhibits triple-specificity phosphatase activity. Biochemical Journal, 2007, 406 (1), pp.13-18. ⟨10.1042/BJ20070670⟩. ⟨hal-00478808⟩