Inhibiting Helicobacter pylori HtrA protease by addressing a computationally predicted allosteric ligand binding site.

ABSTRACT: Helicobacter pylori is associated with inflammatory diseases and can cause gastric cancer and mucosa-associated lymphoma. One of the bacterium's key proteins is high temperature requirement A (HpHtrA) protein, an extracellular serine protease that cleaves E-cadherin of gastric epithelial cells, which leads to loss of cell-cell adhesion. Inhibition of HpHtrA may constitute an intervention strategy against H. pylori infection. Guided by the computational prediction of hypothetical ligand binding sites on the surface of HpHtrA, we performed residue mutation experiments that confirmed the functional relevance of an allosteric region. We virtually screened for potential ligands addressing this surface cleft located between the catalytic and PDZ1 domains. Our r

SUBMITTER: Perna AM 

PROVIDER: S-EPMC4724879 | biostudies-literature | 2014 Jun

REPOSITORIES: biostudies-literature