Molecular basis for the activation of a catalytic asparagine residue in a self-cleaving bacterial autotransporter.

ABSTRACT: Autotransporters are secreted proteins produced by pathogenic Gram-negative bacteria. They consist of a membrane-embedded β-domain and an extracellular passenger domain that is sometimes cleaved and released from the cell surface. We solved the structures of three noncleavable mutants of the autotransporter EspP to examine how it promotes asparagine cyclization to cleave its passenger. We found that cyclization is facilitated by multiple factors. The active-site asparagine is sterically constrained to conformations favorable for cyclization, while electrostatic interactions correctly orient the carboxamide group for nucleophilic attack. During molecular dynamics simulations, water molecules were observed to enter the active site and to form hydrogen bonds favorable for increasing the nucle

SUBMITTER: Barnard TJ 

PROVIDER: S-EPMC3230255 | biostudies-literature | 2012 Jan

REPOSITORIES: biostudies-literature