The structure and mechanism of bacterial type I signal peptidases - A novel antibiotic target

Type I signal peptidases are essential membrane-bound serine proteases that function to cleave the amino-terminal signal peptide extension from protei ns that are translocated across biological membranes. The bacterial signal peptidases are unique serine proteases that utilize a Ser/Lys catalytic dya d mechanism in place of the classical Ser/His/Asp catalytic triad mechanism . They represent a potential novel antibiotic target at the bacterial membr ane surface. This review will discuss the bacterial signal peptidases that have been characterized to date, as well as putative signal peptidase seque nces that have been recognized via bacterial genome sequencing. We review t he investigations into the mechanism of Escherichia coli and Bacillus subti lis signal peptidase, and discuss the results in light of the recent crysta l structure of the E. coil signal peptidase in complex with a P-lactam-type inhibitor. The proposed conserved structural features of Type I signal pep tidases give additional insight into the mechanism of this unique enzyme. ( C) 2000 Elsevier Science Inc. All rights reserved.