Structure of the unliganded form of the proprotein convertase furin suggests activation by a substrate-induced mechanism.

ABSTRACT: Proprotein convertases (PCs) are highly specific proteases required for the proteolytic modification of many secreted proteins. An unbalanced activity of these enzymes is connected to pathologies like cancer, atherosclerosis, hypercholesterolaemia, and infectious diseases. Novel protein crystallographic structures of the prototypical PC family member furin in different functional states were determined to 1.8-2.0 Å. These, together with biochemical data and modeling by molecular dynamics calculations, suggest essential elements underlying its unusually high substrate specificity. Furin shows a complex activation mechanism and exists in at least four defined states: (i) the "off state," incompatible with substrate binding as seen in the unliganded enzyme; (ii) the active "on state" seen in

SUBMITTER: Dahms SO 

PROVIDER: S-EPMC5056075 | biostudies-literature | 2016 Oct

REPOSITORIES: biostudies-literature