The inhibition of type I bacterial signal peptidase: Biological consequences and therapeutic potential.
The general secretory pathway has long been regarded as a potential antibiotic drug target. In particular, bacterial type I signal peptidase (SPase) is emerging as a strong candidate for therapeutic use. In this review, we focus on the information gained from the use of SPase inhibitors as probes of prokaryote biology. A thorough understanding of the consequences of SPase inhibition and the mechanisms of resistance that arise are essential to the success of SPase as an antibiotic target. In addition to the role of SPase in processing secreted proteins, the use of SPase inhibitors has elucidated a previously unknown function for SPase in regulating cleavage events of membrane proteins.
Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
Arryn
A
Craney
Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
Floyd E
FE
Romesberg
D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects* / Q000201:enzymology*; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D008565:Membrane Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008968:Molecular Conformation; D012697:Serine Endopeptidases / Q000378:metabolism
D000900:Anti-Bacterial Agents; D004791:Enzyme Inhibitors; D008565:Membrane Proteins; D012697:Serine Endopeptidases; C026515:type I signal peptidase
Antibiotic; Arylomycin; Protein secretion; SPase; Virulence