Collagen/collagenase interaction: does the enzyme mimic the conformation of its own substrate

ABSTRACT In this report, we present a hypothesis on the mechanism used by interstitial collagenases to cleave their natural substrate, interstitial collagens. The hypothesis is based on the assumption that the proline hinge domain of interstitial collagenase adopts a collagen-like conformation. With a colla-gen-like domain, the enzyme is able to disturb the quaternary orgarnzation of the triple helix in the collagenase-susceptible site. A modeling analysis sug-gests that interaction between prolines of both colla-gen and collagenase forming a kind of “proline zipper ” is involved in the destabilization step. This destabilization makes the three-collagen helix sus-ceptible to the catalytic cleft of the catalyti