title: [Novel inhibitors against the bacterial signal peptidase I].
abstract: New antibiotics with novel modes of action and structures are urgently needed to combat the emergence of multidrug-resistant bacteria. Bacterial signal peptidase I (SPase I) is an indispensable enzyme responsible for cleaving the signal peptide of preprotein to release the matured proteins. Increasing evidence suggests that SPase I plays a crucial role in bacterial pathogenesis by regulating the excretion of a variety of virulent factors, maturation of quorum sensing factor and the intrinsic resistance against beta-lactams. Recently, breakthrough has been achieved in the understanding of three-dimensional structure of SPase I as well as the mechanism of enzyme-inhibitors interaction. Three families of inhibitors are identified, i.e. signal peptide derivatives, beta-lactams and arylomycins. In this article, we summarize the recent advance in the study of structure, activity and structure-activity relationship of SPase I inhibitors.
authors: Institute of Modern Biopharmaceuticals, School of Pharmaceutical Sciences, Southwest University, Chongqing 400716, China.
authors: Guo-Jian
authors: GJ
authors: Liao
authors: Ying
authors: Y
authors: He
authors: Jian-Ping
authors: JP
authors: Xie
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001419:Bacteria / Q000187:drug effects*; D004926:Escherichia coli / Q000187:drug effects; D008565:Membrane Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D009842:Oligopeptides / Q000737:chemistry / Q000494:pharmacology*; D012697:Serine Endopeptidases / Q000378:metabolism; D015842:Serine Proteinase Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D047090:beta-Lactams / Q000037:antagonists & inhibitors*
chemical_list: D000900:Anti-Bacterial Agents; D008565:Membrane Proteins; D009842:Oligopeptides; D015842:Serine Proteinase Inhibitors; C488532:arylomycin A2; D047090:beta-Lactams; D012697:Serine Endopeptidases; C026515:type I signal peptidase