Characterization of a Mycobacterium tuberculosis proteasomal ATPase homologue.

Abstract:

:A screen for Mycobacterium tuberculosis (Mtb) mutants sensitive to reactive nitrogen intermediates identified transposon insertions in the presumptive proteasomal ATPase gene mpa (mycobacterium proteasome ATPase; Rv2115c). mpa mutants are attenuated in both wild type and nitric oxide synthase 2 deficient mice. In this work, we show that attenuation of mpa mutants is severe, and that Mpa is an ATPase associated with various cellular activities (AAA) ATPase that forms hexameric rings resembling the eukaryotic complex p97/valosin-containing protein (VCP). Point mutations in the conserved Walker box ATPase motifs of Mpa greatly reduced or abolished ATPase activity in vitro and abrogated protection of Mtb against acidified nitrite. A mutant Mpa protein missing only its last two amino acids retained ATPase activity, yet failed to protect Mtb against nitrite. The corresponding strain was attenuated in mice. Thus, Mpa is an ATPase whose enzymatic activity is necessary but not sufficient to protect against reactive nitrogen intermediates.

journal_name

Mol Microbiol

journal_title

Molecular microbiology

authors

Darwin KH,Lin G,Chen Z,Li H,Nathan CF

doi

10.1111/j.1365-2958.2004.04403.x

subject

Has Abstract

pub_date

2005-01-01 00:00:00

pages

561-71

issue

2

eissn

0950-382X

issn

1365-2958

pii

MMI4403

journal_volume

55

pub_type

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