The members of the proprotein convertase family play a central role in the processing and/or activation of various protein precursors involved in many physiological processes and various pathologies. The proteolysis of these precursors that occur at basic residues within the general motif (K/R)-(X)-(K/R) is mediated by the proprotein convertases PC1/3, PC2, Furin, PACE4, PC4, PC5 and PC7, where...

The calcium-dependent serine endoproteases prohormone convertase 1/3 (PC1/3) and prohormone convertase 2 (PC2) play important roles in the homeostatic regulation of blood glucose levels, hence implicated in diabetes mellitus. Specifically, the absence of PC2 has been associated with chronic hypoglycemia. Since there is a reasonably good conservation of the catalytic domain between species trans...

The human thyrotropin receptor (TSHR) undergoes proteolytic cleavage closely upstream to amino acid 317. Between residues 261 and 313 are three clusters of positively charged amino acids, arginines (Arg) and lysines (Lys), which are potential subtilisin-related proprotein convertase sites. We used oligonucleotide-directed mutagenesis to perform conservative amino acid substitutions within these...

Familial hypercholesterolaemia (FH) is a common, heritable and preventable cause of premature coronary artery disease. New clinical practice recommendations are presented to assist practitioners in enhancing the care all patients with FH. Core made on detection, diagnosis, assessment management adults, children adolescents Management under-pinned by precepts risk stratification, adherence healt...

The discovery in 2003 that variants in the PCSK9 (proprotein convertase subtilisin/kexin type 9) gene cause autosomal dominant hypercholesterolemia revealed a new aspect of LDL cholesterol (LDL-C) metabolism (1). PCSK9, a protein of 692 amino acid residues produced at high concentrations in the liver, kidney, and intestine, has profound effects on LDL-C concentrations (2). Both gain-of-function...

BACKGROUND Although statin therapy is known to increase concentrations of PCSK9, whether this effect is related to the magnitude of LDL reduction is uncertain. This study was undertaken to understand the extent of this effect and examine the relationship between PCSK9 and LDL cholesterol (LDL-C) reduction. METHODS We measured plasma PCSK9 concentrations by ELISA at baseline and at 1 year in 5...