PDBsum entry 3dpm

Transferase

PDB id

3dpm

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Contents

			Protein chains

					522 a.a. *

			Ligands

					LAS ×2

			Waters ×309

* Residue conservation analysis

PDB id:

3dpm

Links

Name:

Transferase

Title:

Structure of mature cpaf complexed with lactacystin

Structure:

Protein ct_858. Chain: a, b. Fragment: unp residues 25-601. Synonym: cpaf. Engineered: yes

Source:

Chlamydia trachomatis. Organism_taxid: 813. Expressed in: escherichia coli. Expression_system_taxid: 511693.

Resolution:

2.35Å

R-factor:

0.230

R-free:

0.259

Authors:

J.Chai,Z.Huang

Key ref:

Z.Huang et al. (2008). Structural basis for activation and inhibition of the secreted chlamydia protease CPAF. Cell Host Microbe, 4, 529-542. PubMed id: 19064254 DOI: 10.1016/j.chom.2008.10.005

Date:

09-Jul-08

Release date:

13-Jan-09

PROCHECK

	Headers

	References

Protein chains

O84866 (Y858_CHLTR) - Protein CT_858 from Chlamydia trachomatis serovar D (strain ATCC VR-885 / DSM 19411 / UW-3/Cx)

Seq: Struc:

Seq: Struc:					601 a.a. 522 a.a.

Key:

PfamA domain

Secondary structure

DOI no: 10.1016/j.chom.2008.10.005	Cell Host Microbe 4:529-542 (2008)
PubMed id: 19064254

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

20457000

A.F.Kluge, and R.C.Petter (2010).
Acylating drugs: redesigning natural covalent inhibitors.

Curr Opin Chem Biol, 14, 421-427.

20522495

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.

19853923

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.

19388144

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.

19803759

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.

19765998

G.Zhong (2009).
Killing me softly: chlamydial use of proteolysis for evading host defenses.

Trends Microbiol, 17, 467-474.

20090866

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.