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Character sheet with PDB number of proteins and primary reference.
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Title: Storyboards for anti-Proprotein convertase subtilisin kexin 9 (PCSK9) based on Evolocumab, a novel LDL reducing monoclonal antibody
Tools: VMD, Photoshop
Target Audience: Cardiologists (marketing campaign for launching of Evolocumab)
Background: A novel monoclonal antibody therapy targeting proprotein convertase subtilisin kexin 9 to reduce low‐density lipoprotein cholesterol (LDL). PCSK9 is an enzyme that impairs LDL clearance from the plasma by promoting LDL receptor degradation. PCSK9 binds to LDL receptors present on the surface of hepatocytes (liver cells). When PCSK9 binds an LDL receptor, the latter is taken into the cell and degraded. This in turn leaves fewer LDL receptors available on hepatocytes to remove excess LDL from the blood. Amgen and Sanofi/Regeneron have FDA approved PCSK9 therapies
References
Harris LJ, Larson SB, Hasel KW, McPherson A. Refined structure of an intact IgG2a monoclonal antibody. Biochemistry. 1997;36(7):1581-1597.
Huang S, Henry L, Ho YK, Pownall HJ, Rudenko G. Mechanism of LDL binding and release probed by structure-based mutagenesis of the LDL receptor. J Lipid Res. 2010;51(2):297-308. doi:10.1194/jlr.M000422.
Lambert G, Sjouke B, Choque B, Kastelein JJ, Hovingh GK. The PCSK9 decade. J Lipid Res. 2012;53(12):2515-2524.
Nikolac N. Lipemia: causes, interference mechanisms, detection and management. Biochemia Medica. 2014;24(1):57-67. doi:10.11613/BM.2014.008.
Peterson AS, Fong LG, Young SG. PCSK9 function and physiology. J Lipid Res. 2008;49(7):1595-1599.