[HTML][HTML] Stepwise processing analyses of the single-turnover PCSK9 protease reveal its substrate sequence specificity and link clinical genotype to lipid phenotype
JS Chorba, AM Galvan, KM Shokat - Journal of Biological Chemistry, 2018 - ASBMB
Proprotein convertase subtilisin/kexin type 9 (PCSK9) down-regulates the low-density
lipoprotein (LDL) receptor, elevating LDL cholesterol and accelerating atherosclerotic heart
disease, making it a promising cardiovascular drug target. To achieve its maximal effect on
the LDL receptor, PCSK9 requires autoproteolysis. After cleavage, PCSK9 retains its
prodomain in the active site as a self-inhibitor. Unlike other proprotein convertases,
however, this retention is permanent, inhibiting any further protease activity for the …
lipoprotein (LDL) receptor, elevating LDL cholesterol and accelerating atherosclerotic heart
disease, making it a promising cardiovascular drug target. To achieve its maximal effect on
the LDL receptor, PCSK9 requires autoproteolysis. After cleavage, PCSK9 retains its
prodomain in the active site as a self-inhibitor. Unlike other proprotein convertases,
however, this retention is permanent, inhibiting any further protease activity for the …