 |
|
|
|
|
|
 |
Contents |
 |
|
|
|
|
|
|
|
|
* Residue conservation analysis
|
|
|
|
|
|
|
|
|
|
|
|
Gene Ontology (GO) functional annotation
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Biological process
|
proteolysis
|
1 term
|
|
|
Biochemical function
|
serine-type peptidase activity
|
1 term
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
|
|
|
|
|
|
| |
|
|
Cell Host Microbe
4:529-542
(2008)
|
|
PubMed id:
|
|
|
|
|
|
| |
|
Structural basis for activation and inhibition of the secreted chlamydia protease CPAF.
|
|
Z.Huang,
Y.Feng,
D.Chen,
X.Wu,
S.Huang,
X.Wang,
X.Xiao,
W.Li,
N.Huang,
L.Gu,
G.Zhong,
J.Chai.
|
|
|
|
|
| |
ABSTRACT
|
|
|
|
| |
|
|
The obligate intracellular pathogen Chlamydia trachomatis is the most common
cause of sexually transmitted bacterial disease. It secretes a protease known as
chlamydial protease/proteasome-like activity factor (CPAF) that degrades many
host molecules and plays a major role in Chlamydia pathogenesis. Here, we show
that mature CPAF is a homodimer of the catalytic domains, each of which
comprises two distinct subunits. Dormancy of the CPAF zymogen is maintained by
an internal inhibitory segment that binds the CPAF active site and blocks its
homodimerization. CPAF activation is initiated by trans-autocatalytic cleavage,
which induces homodimerization and conformational changes that assemble the
catalytic triad. This assembly leads to two autocatalytic cleavages and removal
of the inhibitory segment, enabling full CPAF activity. CPAF is covalently bound
and inhibited by the proteasome inhibitor lactacystin. These results reveal the
activation mechanism of the CPAF serine protease and suggest new opportunities
for anti-Chlamydia drug development.
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
 |
 |
|
Literature references that cite this PDB file's key reference
|
|
|
| |
PubMed id
|
|
Reference
|
|
|
|
|
|
A.F.Kluge,
and
R.C.Petter
(2010).
Acylating drugs: redesigning natural covalent inhibitors.
|
| |
Curr Opin Chem Biol, 14,
421-427.
|
|
|
|
|
|
|
D.Chen,
L.Lei,
C.Lu,
R.Flores,
M.P.DeLisa,
T.C.Roberts,
F.E.Romesberg,
and
G.Zhong
(2010).
Secretion of the chlamydial virulence factor CPAF requires the Sec-dependent pathway.
|
| |
Microbiology, 156,
3031-3040.
|
|
|
|
|
|
|
A.K.Murthy,
M.N.Guentzel,
G.Zhong,
and
B.P.Arulanandam
(2009).
Chlamydial protease-like activity factor--insights into immunity and vaccine development.
|
| |
J Reprod Immunol, 83,
179-184.
|
|
|
|
|
|
|
D.Chen,
J.Chai,
P.J.Hart,
and
G.Zhong
(2009).
Identifying catalytic residues in CPAF, a Chlamydia-secreted protease.
|
| |
Arch Biochem Biophys, 485,
16-23.
|
|
|
|
|
|
|
D.D.Rockey,
J.Wang,
L.Lei,
and
G.Zhong
(2009).
Chlamydia vaccine candidates and tools for chlamydial antigen discovery.
|
| |
Expert Rev Vaccines, 8,
1365-1377.
|
|
|
|
|
|
|
G.Zhong
(2009).
Killing me softly: chlamydial use of proteolysis for evading host defenses.
|
| |
Trends Microbiol, 17,
467-474.
|
|
|
|
|
|
|
J.Sun
(2009).
Pathogenic Bacterial Proteins and their Anti-Inflammatory Effects in the Eukaryotic Host.
|
| |
Antiinflamm Antiallergy Agents Med Chem, 8,
214-227.
|
|
|
|
|
|
The most recent references are shown first.
Citation data come partly from CiteXplore and partly
from an automated harvesting procedure. Note that this is likely to be
only a partial list as not all journals are covered by
either method. However, we are continually building up the citation data
so more and more references will be included with time.
|
|
Links
