Many secreted proteins require cleavage by proprotein convertases (PCs) for maturation and eventually activation. Furin and PC7 are both PCs – with Furin being a serine protease with stringent specificity for multibasic cleavage motifs. It prefers to cut after the consensus sequence R-X-(K/R)-R↓ (X is any amino acid and ↓ represents the cutting site).
Furin is ubiquitously expressed, a feature which is used by many bacterial and viral pathogens to hijack this protease for activation of their own toxins and surface proteins. Acquisition of a Furin activation site is regarded as a main virulence factor of highly pathogenic virus strains like HIV, RSV and the measles virus. Another viral Furin substrate protein is the spike (S) protein of the SARS-CoV-2 virus, a virus which causes the disease COVID-19 and is responsible for over 5 million deaths worldwide during the recent pandemic. Thus, Furin inhibitors are promising antiviral compounds and are intensively investigated in structure based drug design. A key challenge is the development of Furin specific inhibitors i.e. that do not inhibit other PC isoforms like PC7, to reduce potential side effects.
Figure 1: X-ray structure of Furin with a substrate like inhibitor. A) Furin and the inhibitor are shown as cartoon representation and ball-and-stick model. B) The molecular surface of the substrate binding pocket (rectangular framed region in A) is colored according to the electrostatic potential. The inhibitor is given as stick model.
Jena Bioscience offers recombinant Furin and PC7 produced as soluble proteins in a human cell line resulting in intact glycosylation. Our recombinant Furin is suited for applications related to inhibitor development, including enzyme kinetics and biochemical assays. The fully activated recombinant PC7 can be used to test the specificity of PC inhibitors. Furin and PC7 can be applied for in vitro activation of substrates and for cleavage assays with substrate proteins.
| Product | Cat. No. | Amount | Price |
|---|---|---|---|
| Furin Proprotein Convertase Subtilisin/Kexin Type 3 (PCSK3) human, recombinant, human cell line HEK293S |
PR-968S | 10 µg | 607,70 € |
| PR-968L | 5 x 10 µg | 2.430,60 € | |
| PC7 Proprotein Convertase Subtilisin/Kexin Type 7 (PCSK7) human, recombinant, human cell line HEK293S |
PR-969S | 2000 U | 499,10 € |
| PR-969L | 5 x 2.000 U | 1.996,20 € |
Dahms et al. (2014) X-ray Structures of Human Furin in Complex with Competitive Inhibitors. ACS Chem. Biol. 9 (5):1113.
Dahms et al. (2018) X-ray Structures of the Proprotein Convertase Furin Bound with Substrate Analogue Inhibitors Reveal Substrate Specificity Determinants beyond the S4 Pocket. Biochemistry 57 (6):925.
Dahms et al. (2021) OFF-State-Specific Inhibition of the Proprotein Convertase Furin. ACS Chem. Biol. 16 (9):1692.
