TMPRSS2 enzymatic activity

Excerpt

Transmembrane protease serine 2 (TMPRSS2) is a type II transmembrane serine protease that is expressed and self-cleaved from the surface of epithelial cells in a variety of tissues. Although the biological function of TMPRSS2 remains unclear, it is believed to serve as an initiator protease in the extracellular matrix (ECM). Regulated through the androgen receptor, TMPRSS2 is most notable as a genetic translocation fusion with the ERG transcription factor in many prostate cancers. However, TMPRSS2 has more recently been shown to play a role in SARS-CoV2 S (spike) protein priming following ACE2 binding, contributing to viral-host membrane fusion and subsequent infection. Previously, in vivo mouse models for SARS-CoV and MERS-CoV with a TMPRSS2 gene knockout caused a reduction in lung pathology after viral infection while not seeing any effect on development or survival, which supports TMPRSS2 as a suitable target for therapeutic development. This enzymatic assay will serve to monitor activity of human TMPRSS2 and facilitate detection of small molecules with the potential to disrupt endogenous enzyme function.