Crystal structure of the outer membrane protease OmpT from Escherichia coli suggests a novel catalytic site

OmpT from Escherichia coli belongs to a family of highly homologous outer m embrane proteases, known as omptins, which are implicated in the virulence of several pathogenic Gram-negative bacteria. Here we present the crystal s tructure of OmpT, which shows a 10-stranded antiparallel beta -barrel that protrudes far from the lipid bilayer into the extracellular space. We ident ified a putative binding site for lipopolysaccharide, a molecule that is es sential for OmpT activity. The proteolytic site is located in a groove at t he extracellular top of the vase-shaped beta -barrel. Based on the constell ation of active site residues, we propose a novel proteolytic mechanism, in volving a His-Asp dyad and an Asp-Asp couple that activate a putative nucle ophilic water molecule. The active site is fully conserved within the ompti n family. Therefore, the structure described here provides a sound basis fo r the design of drugs against omptin-mediated bacterial pathogenesis. Coord inates are in the Protein Data Bank (accession No. 1178).