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:4.1.2.42 (
DTA
)
1,693
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Bacillus anthracis lethal toxin consists of the protective antigen (PA) and the
metalloprotease
lethal factor (LF). During cellular uptake PA forms pores in membranes of endosomes, and unfolded LF translocates through the pores into the cytosol. We have investigated whether host cell chaperones facilitate translocation of LF and the fusion protein LF(N)
DTA
. LF(N) mediates uptake of LF(N)
DTA
into the cytosol, where
DTA
, the catalytic domain of diphtheria toxin, ADP-ribosylates elongation factor-2, allowing for detection of small amounts of translocated LF(N)
DTA
. Cyclosporin A, which inhibits peptidyl-prolyl cis/trans isomerase activity of cyclophilins, and radicicol, which inhibits Hsp90 activity, prevented uptake of LF(N)
DTA
into the cytosol of CHO-K1 cells and protected cells from intoxication by LF(N)
DTA
/PA. Both inhibitors, as well as an antibody against cyclophilin A blocked the release of active LF(N)
DTA
from endosomal vesicles into the cytosol in vitro. In contrast, the inhibitors did not inhibit cellular uptake of LF. In vitro, cyclophilin A and Hsp90 bound to LF(N)
DTA
and
DTA
but not to LF, implying that
DTA
determines this interaction. In conclusion, cyclophilin A and Hsp90 facilitate translocation of LF(N)
DTA
, but not of LF, across endosomal membranes, and thus they function selectively in promoting translocation of certain proteins, but not of others.
...
PMID:Role of CypA and Hsp90 in membrane translocation mediated by anthrax protective antigen. 2094 44
