Ligases

E3 ligases are the enzymes responsible for conjugating multiple ubiquitin molecules (poly-ubiquitin), one ubiquitin at a time, to specific target proteins, directing the target proteins to the proteasome for degradation. In some cases the E3 ligase receives ubiquitin from the E2 enzyme and transfers it to the target protein; in other cases it acts by interacting with both the E2 enzyme and the substrate but does not directly receive ubiquitin. The attachment of ubiquitin by E3 ligases to target proteins plays a crucial and essential role in many key regulatory processes in the cell. There are approximately 600 different E3 ligases in the human proteome, many of which have been associated with diseases including cancer, Parkinson's Disease, osteoporosis, muscle degeneration, and diabetes. Like deubiquitylases, many E3 ligases are considered novel targets for drug discovery or design.

Ligase Technology platform

Although pharmaceutical companies have been trying to identify specific inhibitors for E3 ligases of therapeutic interest, to date few, if any, clinical candidates have emerged. Progenra scientists have recently developed and filed a patent for a novel and superior assay technology that can detect ubiquitination catalysed by any of the approximately 600 known E3 ligases. Screening has commenced, and new E3 ligase inhibitors are being evaluated for various therapeutic applications.[Cold Spring Harbor- The Ubiquitin Family, and The Ubiquitin Workshop.]

Benefits:

Rapid and robust readout
Non-radioactive components
Miniaturization to multiwell format
Auto- or substrate ubiquitylation
Modular; works for all E3 ligases tested