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Chlamydia protease-like activity factor (CPAF): characterization of proteolysis activity in vitro and development of a nanomolar affinity CPAF zymogen-derived inhibitor.

Maria M MM Bednar, Ine I Jorgensen, Raphael H RH Valdivia, and Dewey G DG McCafferty

Biochemistry 50(35):7441-3 (2011) PMID 21830778

During infection of epithelial cells, the obligate intracellular pathogen Chlamydia trachomatis secretes the serine protease Chlamydia protease-like activity factor (CPAF) into the host cytosol to regulate a range of host cellular processes through targeted proteolysis. Here we report the development of an in vitro assay for the enzyme and the discovery of a cell-permeable CPAF zymogen-based peptide inhibitor with nanomolar inhibitory affinity. Treating C. trachomatis-infected HeLa cells with this inhibitor prevented CPAF cleavage of the intermediate filament vimentin and led to the loss of vimentin cage surrounding the intracellular vacuole. Because Chlamydia is a genetically intractable organism, this inhibitor may serve as a tool for understanding the role of CPAF in pathogenesis.

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