3DPN

Crystal Structure of cpaf s499a mutant

Summary for 3DPN

• Entry DOI: 10.2210/pdb3dpn/pdb
• Related: 3DJA 3DOR 3DPM
• Descriptor: Protein CT_858 (1 entity in total)
• Functional Keywords: cpaf, s499a, zymogen, transferase
• Biological source: Chlamydia trachomatis
• Total number of polymer chains: 2
• Total formula weight: 130757.66

Authors

Chai, J.,Huang, Z. (deposition date: 2008-07-09, release date: 2009-01-13, Last modification date: 2023-11-01)

Primary citation

Huang, Z.,Feng, Y.,Chen, D.,Wu, X.,Huang, S.,Wang, X.,Xiao, X.,Li, W.,Huang, N.,Gu, L.,Zhong, G.,Chai, J.
Structural basis for activation and inhibition of the secreted chlamydia protease CPAF
Cell Host Microbe, 4:529-542, 2008

PubMed 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.

PubMed: 19064254
DOI: 10.1016/j.chom.2008.10.005

Experimental method

X-RAY DIFFRACTION (3.3 Å)