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PDBsum entry 3dpm
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References listed in PDB file
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Key reference
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Title
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Structural basis for activation and inhibition of the secreted chlamydia protease cpaf.
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Authors
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Z.Huang,
Y.Feng,
D.Chen,
X.Wu,
S.Huang,
X.Wang,
X.Xiao,
W.Li,
N.Huang,
L.Gu,
G.Zhong,
J.Chai.
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Ref.
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Cell Host Microbe, 2008,
4,
529-542.
[DOI no: ]
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PubMed id
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Abstract
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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.
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