United Kingdom (UK)
Recombinant monoclonal antibody to PCSK9. Manufactured using AbAb’s Recombinant Platform with variable regions (i.e. specificity) from the hybridoma 6E2.
UniProt Accession Number of Target Protein: Q8NBP7
Alternative Name(s) of Target: NARC1; NARC-1; PC9; Proprotein convertase subtilisin/kexin type; Neural apoptosis-regulated convertase 1; Proprotein convertase 9; Subtilisin/kexin-like protease PC9; Ab6E2
Immunogen: The original antibody was generated by immunization of PCSK9 knock-out mice with recombinant human PCSK9.
Specificity: This antibody binds a helical conformational epitope formed by the acidic amino acid stretch comprising amino acids between Q31-A53 of the human PCSK9, particularly the segment 'DYEELVLAL'. It can bind intact human PCSK9 but can not bind mouse PCSK9. Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a serine protease enzyme encoded by the PCSK9 gene in humans and it plays a role in regulation of circulating cholesterol. It is associated with autosomal dominant hypercholesterolemia, a state of elevated levels of LDL (low-density lipoprotein) cholesterol. Autosomal dominant hypercholesterolemia can result in severe implications such as stroke and coronary heart disease.
Application Notes: Proprotein convertase subtilisin/kexin type 9 (PCSK9) regulates serum LDL cholesterol (LDL-C) by interacting with the LDL receptor (LDLR) and is an attractive therapeutic target for LDL-C lowering. The epitope mapping of this antibody was done using western blotting. This antibody was able to identify a 16 kDa prodomain of recombinant PCSK9 but not the 60 kDa band comprising the catalytic and C-terminal domain in western blot. Surface plasmon resonance demonstrated that Ab6E2 (IgG1) bound to PCSK9 with a KD of 10.5 ± 1.2 nM. Biolayer interferometry experiments suggested that the formation of proper α-helix is required for the binding interaction of this antibody. This antibody was also used for immunoprecipitation of secreted native PCSK9 from HepG2, IM-95m and H2073 cell l ins and of recombinant PCSK9 (PMID: 30653992).
Antibody first published in:
Ultsch et al. Identification of a Helical Segment within the Intrinsically Disordered Region of the PCSK9 Prodomain. J Mol Biol. 2019 Mar 1;431(5):885-903. PMID:30653992
Note on publication:
Describes the generation and epitope mapping of this antibody.