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

EMBO J. 2001 Sep 17;20(18):5033-9. doi: 10.1093/emboj/20.18.5033.


OmpT from Escherichia coli belongs to a family of highly homologous outer membrane proteases, known as omptins, which are implicated in the virulence of several pathogenic Gram-negative bacteria. Here we present the crystal structure of OmpT, which shows a 10-stranded antiparallel beta-barrel that protrudes far from the lipid bilayer into the extracellular space. We identified a putative binding site for lipopolysaccharide, a molecule that is essential for OmpT activity. The proteolytic site is located in a groove at the extracellular top of the vase-shaped beta-barrel. Based on the constellation of active site residues, we propose a novel proteolytic mechanism, involving a His-Asp dyad and an Asp-Asp couple that activate a putative nucleophilic water molecule. The active site is fully conserved within the omptin family. Therefore, the structure described here provides a sound basis for the design of drugs against omptin-mediated bacterial pathogenesis. Coordinates are in the Protein Data Bank (accession No. 1I78)

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Aspartic Acid / chemistry
  • Binding Sites
  • Catalytic Domain
  • Crystallography, X-Ray
  • Escherichia coli / enzymology*
  • Histidine / chemistry
  • Lipopolysaccharides / metabolism
  • Models, Molecular
  • Molecular Sequence Data
  • Protein Structure, Tertiary
  • Sequence Homology, Amino Acid
  • Serine Endopeptidases / chemistry*
  • Serine Endopeptidases / metabolism


  • Lipopolysaccharides
  • Aspartic Acid
  • Histidine
  • Serine Endopeptidases
  • omptin outer membrane protease

Associated data

  • PDB/1I78