PCSK9-DyLight™ 633

Proprotein convertase subtilisin kexin 9 (PCSK9) is a zymogen and member of the subtilisin serine protease family that reduces protein levels of LDL receptors (LDLRs), the receptor for LDL-cholesterol (LDL-C).^1,2 It is primarily expressed in the liver and is composed of an N-terminal prodomain that regulates PCSK9 maturation, a catalytic domain containing a catalytic aspartic acid-histidine-serine triad, and a C-terminal domain that contains the LDLR binding site.^3,4,2 PCSK9 is synthesized as a proprotein that is autocatalytically cleaved to generate the 63 kDa mature protein in which the N-terminal prodomain remains non-covalently bound to the catalytic domain to inhibit further activity.⁴ The mature PCSK9 is secreted and circulates in the plasma where it binds to cell surface-expressed LDLRs, triggering endocytosis and lysosomal degradation of the PCSK9-LDLR complex.² This action decreases LDLR expression and reduces cellular LDL-C uptake. Gain-of-function and loss-of-function PCSK9 mutations have been associated with autosomal dominant hypercholesterolemia and decreased plasma LDL-C levels, respectively, in humans.² Reducing the activity of circulating PCSK9 with monoclonal antibodies or small molecule inhibitors decreases LDL-C levels and reduces the risk of adverse cardiovascular events in individuals with hypercholesterolemia. Cayman's PCSK9-DyLight™ 633 is synthesized as a 75.8 kDa proprotein. After cleavage of the signal peptide (1-30 aa) PCKS9 autocatalytically cleaves to the 13.8 kDa prodomain (aa 31-152) and the 59 kDa mature form (aa 153-692 + 10x His-tag). It can be used for cell-based assays.

WARNING This product is not for human or veterinary use.

1. Maxwell, K.N., Fisher, E.A., and Breslow, J.L. Overexpression of PCSK9 accelerates the degradation of the LDLR in a post-endoplasmic reticulum compartment. Proc. Natl. Acad. Sci. USA 102(6), 2069-2074 (2005).

2. Schulz, R., Schlüter, K.-D., and Laufs, U. Molecular and cellular function of the proprotein convertase subtilisin/kexin type 9 (PCSK9). Basic Res. Cardiol. 110(2), 4 (2015).

3. Seidah, N.G., Benjannet, S., Wickham, L., et al. The secretory proprotein convertase neural apoptosis-regulated convertase 1 (NARC-1): Liver regeneration and neuronal differentiation. Proc. Natl. Acad. Sci. USA 100(3), 928-933 (2003).

4. Burke, A.C., Dron, J.S., Hegele, R.A., et al. PCSK9: Regulation and target for drug development for dyslipidemia. Annu. Rev. Pharmacol. Toxicol. 57, 223-244 (2017).