[HTML][HTML] The proprotein convertase subtilisin/kexin type 9 (PCSK9) active site and cleavage sequence differentially regulate protein secretion from proteolysis
JS Chorba, KM Shokat - Journal of Biological Chemistry, 2014 - ASBMB
Biologic-based strategies to inhibit proprotein convertase subtilisin/kexin type 9 (PCSK9)
show promise as anti-hypercholesterolemic and, therefore, anti-atherosclerotic therapies.
Despite substantial effort, no small molecule strategy to inhibit PCSK9 has demonstrated
feasibility. In this study we interrogated the chemistry of the PCSK9 active site and its
adjacent residues to identify a foothold with which to drug the PCSK9 processing pathway
and ultimately disrupt the interaction with the LDL receptor. Here, we develop a system in …
show promise as anti-hypercholesterolemic and, therefore, anti-atherosclerotic therapies.
Despite substantial effort, no small molecule strategy to inhibit PCSK9 has demonstrated
feasibility. In this study we interrogated the chemistry of the PCSK9 active site and its
adjacent residues to identify a foothold with which to drug the PCSK9 processing pathway
and ultimately disrupt the interaction with the LDL receptor. Here, we develop a system in …
