Using computational and experimental approaches to understand protein function: application to proprotein convertases and other disease-related proteins

This thesis describes the combination of biochemical, biophysical, and computational tools to investigate the mechanism of pH-mediated activation of proprotein convertases. Proprotein convertases are a family of human serine endoproteases that are involved in processing of hormones, enzymes, and receptors. In order to spatiotemporally control this processing in distinct organelles of the secretory pathway proprotein convertases have evolved to sense the pH of the correct organelle to mediate activation.