Premium
Nucleoside diphosphate kinase of Mycobacterium tuberculosis acts as GTPase‐activating protein for Rho‐GTPases
Author(s) -
Chopra Puneet,
Koduri Harshavardhan,
Singh Ramandeep,
Koul Anil,
Ghildiyal Megha,
Sharma Kirti,
Tyagi Anil K,
Singh Yogendra
Publication year - 2004
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2004.06.073
Subject(s) - gtpase , nucleoside diphosphate kinase , gtp' , gtpase activating protein , microbiology and biotechnology , guanine nucleotide exchange factor , effector , biochemistry , biology , autophosphorylation , kinase , gtp binding protein regulators , chemistry , g protein , protein kinase a , signal transduction , enzyme
Several bacterial pathogens secrete proteins into the host cells that act as GTPase‐activating proteins (GAPs) for Rho‐GTPases and convert GTP‐bound active form to GDP‐bound inactive form. However, no such effector molecule has been identified in Mycobacterium tuberculosis . In this study, we show that culture supernatant of M. tuberculosis H 37 Rv harbors a protein that stimulates the conversion of GTP‐bound Rho‐GTPases to the GDP‐bound form. Nucleoside diphosphate kinase (Ndk) was identified as this culture supernatant protein that stimulated in vitro GTP hydrolysis by members of Rho‐GTPases. The histidine‐117 mutant of Ndk, which is impaired for autophosphorylation and nucleotide‐binding activities, shows GAP activity. These results suggest that Ndk of M. tuberculosis functions as a Rho‐GAP to downregulate Rho‐GTPases, and this activity may aid in pathogenesis of the bacteria.