CircuLex PCSK9-LDLR in vitro Binding Assay Kit

  • Target PCSK9-LDLR
  • Code # CY-8150
  • Size 96 Assays
  • Price

Alternative Names

proprotein convertase subtilisin, kexin type 9, NARC-1, FH3


PCSK9 (also known as neural apoptosis-regulated convertase, NARC-1) is a 692-residue extracellular protein expressed primarily in the kidneys, liver and intestines (1) representing the 9th member of the secretory subtilase family. Various genetic observations subsequently mapped PCSK9 as the third gene (along with LDLR and APOB) to cause autosomal dominant hypercholesterolemia (ADH). These studies suggested that gain of function mutations increase plasma levels of LDL-c (2–6), whereas nonsense or missense (loss-of-function) mutations, which interfere with folding or secretion of PCSK9, lead to a reduction of plasma levels of LDL-c and an 88% decrease in the risk of coronary heart disease (CHD) (5). In mice, adenoviral overexpression of PCSK9 results in increased plasma LDL-c level in normal mice but not in LDLR-deficient mice (7). Deletion of PCSK9 causes an increase in level of LDLR protein but not mRNA (8). These findings lead to a hypothesis that PCSK9 exerts its role in cholesterol metabolism through posttranslational down-regulation of LDLR, the receptor responsible for clearing LDL-c from plasma. Evidence is consistent with the secreted form of PCSK9 binding directly to the LDLR and resulting in degradation of the receptor (9, 10). Zhang et al. (11) localized the binding site of PCSK9 in the LDLR to the first epidermal growth factor-like repeat (EGF-A) of the extracellular domain and showed that PCSK9 binding to this site is required for LDLR degradation. In light of these observations and the fact that PCSK9 in the circulation may cause the degradation of hepatic LDLR in the liver, PCSK9 would seem to be an attractive drug target for lowering LDLC.
  • Components:
    • Microplate
    • Recombinant His-tagged PCSK9 wild type
    • Biotinylated anti-His-tag monoclonal antibody
    • Reaction Buffer
    • HRP-conjugated Streptavidin
    • Conjugate Dilution Buffer
    • 10X Wash Buffer
    • Substrate Reagent
    • Stop Solution
  • Description:
    The CycLex Research Product CircuLex PCSK9-LDLR in vitro Binding Assay Kit can be used for screening inhibitors of PCSK9-LDLR interaction in vitro.
  • Product Type:
  • Short Description:

    CircuLex PCSK9-LDLR in vitro Binding Assay Kit.

  • Size:
    96 Assays
  • Storage Temperature:
  • Target:
  1. (Yonsei Med J 2015 Jul 29)
  1. Seidah NG, Benjannet S, Wickham L, Marcinkiewicz J, Jasmin SB, Stifani S, Basak A, Prat A, Chretien M (2003) Proc Natl Acad Sci USA 100:928–933.
  2. Abifadel M, Varret M, Rabes JP, Allard D, Ouguerram K, Devillers M, Cruaud C, Benjannet S, Wickham L, Erlich D, et al. (2003) Nat Genet 34:154–156.
  3. Leren TP (2004) Clin Genet 65:419–422.
  4. Allard D, Amsellem S, Abifadel M, Trillard M, Devillers M, Luc G, Krempf M, Reznik Y, Girardet JP, Fredenrich A, et al. (2005) Hum Mutat 26:497.
  5. Cohen JC, Boerwinkle E, Mosley TH, Jr, Hobbs HH (2006) N Engl J Med 354, 1264–1272.
  6. Berge KE, Ose L, Leren TP (2006) Arterioscler Thromb Vasc Biol 26:1094–1100.
  7. Maxwell KN, Breslow JL (2004) Proc Natl Acad Sci USA 101:7100–7105.
  8. Rashid S, Curtis DE, Garuti R, Anderson NN, Bashmakov Y, Ho YK, Hammer RE, Moon YA, Horton JD (2005) Proc Natl Acad Sci USA 102:5374–5379.
  9. Lagace, T. A., Curtis, D. E., Garuti, R., McNutt, M. C., Park, S. W., Prather, H. B., Anderson, N. N., Ho, Y. K., Hammer, R. E., and Horton, J. D. (2006) J. Clin. Investig. 116, 2995–3005
  10. Cameron, J., Holla, O. L., Ranheim, T., Kulseth, M. A., Berge, K. E., and Leren, T. P. (2006) Hum. Mol. Genet. 15, 1551–1558
  11. Zhang, D. W., Lagace, T. A., Garuti, R., Zhao, Z., McDonald, M., Horton, J. D., Cohen, J. C., and Hobbs, H. H. (2007) J. Biol. Chem. 282, 18602–18612