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Insights into a PCSK9 structural groove: a harbinger of new drugs to reduce LDL-cholesterol

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PCSK9 enhances LDL cholesterol (LDL-c) levels by escorting the liver LDL receptor (LDLR) to endosomes and lysosomes for degradation. PCSK9 monoclonal antibodies and RNA-antisense formulations are effective in reducing LDL cholesterol in patients. The recent structural identification of a novel pocket in PCSK9 paves the way to the future development of orally active small-molecule hypocholesterolemic drugs.

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Figure 1: Inhibition of the PCSK9-induced LDLR degradation.

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Acknowledgements

This work was supported by the CIHR grants Foundation Scheme #148363, a Canada Research Chair #231335, and a Fondation Leducq grant #13CVD03. The author acknowledges the expert contribution of E. Girard.

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Authors and Affiliations

  1. the Laboratory of Biochemical Neuroendocrinology, Clinical Research Institute of Montreal, Montreal, Quebec, Canada

    Nabil G Seidah

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  1. Nabil G Seidah
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Correspondence to Nabil G Seidah.

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Seidah, N. Insights into a PCSK9 structural groove: a harbinger of new drugs to reduce LDL-cholesterol. Nat Struct Mol Biol 24, 785–786 (2017). https://doi.org/10.1038/nsmb.3471

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