RC1339/APRc from Is a Novel Aspartic Protease with Properties of Retropepsin-Like Enzymes

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Several rickettsiae are pathogenic to humans by causing severe infections, including epidemic typhus (Rickettsia prowazekii), Rocky Mountain spotted fever (Rickettsia rickettsii), and Mediterranean spotted fever (Rickettsia conorii). Progress in correlating rickettsial genes and gene functions has been greatly hampered by the intrinsic difficulty in working with these obligate intracellular bacteria, despite the increasing insights into the mechanisms of pathogenesis of and the immune response to rickettsioses. Therefore, comparison of the multiple available genomes of Rickettsia is proving to be the most practical method to identify new factors that may play a role in pathogenicity. Here, we identified and characterized a novel retropepsin-like enzyme, APRc, that is expressed by at least two pathogenic rickettsial species, R. conorii and R. rickettsii. We have also established that APRc acts to process two major surface antigen/virulence determinants (OmpB/Sca5, OmpA/Sca0) in vitro and we suggest that this processing event is important for protein function. We demonstrate that APRc is specifically inhibited by drugs clinically used to treat HIV infections, providing the exciting possibility of targeting this enzyme for therapeutic intervention. With this work, we demonstrate that retropepsin-type aspartic proteases are indeed present in prokaryotes, suggesting that these enzymes may represent an ancestral form of these proteases.

Vyšlo v časopise: RC1339/APRc from Is a Novel Aspartic Protease with Properties of Retropepsin-Like Enzymes. PLoS Pathog 10(8): e32767. doi:10.1371/journal.ppat.1004324
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004324

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