title: Bacterial proteolytic complexes as therapeutic targets.
abstract: Proteases have been successfully targeted for the treatment of several diseases, including hypertension, type 2 diabetes, multiple myeloma, HIV and hepatitis C virus infections. Given the demonstrated pharmacological tractability of this enzyme family and the pressing need for novel drugs to combat antibiotic resistance, proteases have also attracted interest as antibacterial targets--particularly the widely conserved intracellular bacterial degradative proteases, which are often indispensable for normal bacterial growth or virulence. This Review summarizes the roles of the key prokaryotic degradative proteases, with a focus on the initial efforts and associated challenges in developing specific therapeutic modulators of these enzymes as novel classes of antibacterial drugs.
authors.affiliation: Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, Massachusetts                 02138, USA.
authors.forename: Ravikiran M
authors.initials: RM
authors.lastname: Raju
authors.forename: Alfred L
authors.initials: AL
authors.lastname: Goldberg
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Rubin
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000378:metabolism*; D018360:Crystallography, X-Ray; D016503:Drug Delivery Systems / Q000379:methods*; D006801:Humans; D010447:Peptide Hydrolases / Q000737:chemistry* / Q000378:metabolism*; D059748:Proteolysis / Q000187:drug effects
chemical_list: D000900:Anti-Bacterial Agents; D010447:Peptide Hydrolases