Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:1.6.3.1 (
NADPH oxidase
)
11,281
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Mycobacterium tuberculosis
employs defense mechanisms to protect itself from reactive oxygen species (ROS)-mediated cytotoxicity inside macrophages. In the current study, we found that a secretory protein of
M. tuberculosis
PPE2
disrupted the assembly of
NADPH oxidase
complex.
PPE2
inhibited
NADPH oxidase
-mediated ROS generation in RAW 264.7 macrophages and peritoneal macrophages from BALB/c mice.
PPE2
interacted with the cytosolic subunit of
NADPH oxidase
, p67
phox
, and prevented translocation of p67
phox
and p47
phox
to the membrane, resulting in decreased
NADPH oxidase
activity. Trp236 residue present in the SH3-like domain of
PPE2
was found to be critical for its interaction with p67
phox
Trp236Ala mutant of
PPE2
did not interact with p67
phox
and thereby did not affect ROS generation.
M. tuberculosis
expressing
PPE2
and
PPE2
-null mutants complemented with
PPE2
survived better than
PPE2
-null mutants in infected RAW 264.7 macrophages. Altogether, this study suggests that
PPE2
inhibits
NADPH oxidase
-mediated ROS production to favor
M. tuberculosis
survival in macrophages. The findings that
M. tuberculosis
PPE2
protein is involved in the modulation of oxidative response in macrophages will help us in improving our knowledge of host-pathogen interactions and the application of better therapeutics against tuberculosis.
...
PMID:
Mycobacterium tuberculosis
PPE2 Protein Interacts with p67
phox
and Inhibits Reactive Oxygen Species Production. 3137 44
