Endoproteinase-protein inhibitor interactions

Nature uses protein inhibitors as important tools to regulate the proteolyt ic activity of their target proteinases. Most of these inhibitors for which 3D structures are available are directed towards serine proteinases, inter acting with their active-sites in a substrate-like "canonical" manner via a n exposed reactive-site loop of conserved conformation. More recently, some non-canonically binding serine proteinase inhibitors, two cysteine protein ase inhibitors, and three zinc endopeptidase inhibitors have been character ized in the free and complexed state, displaying novel mechanisms of inhibi tion with their target proteinases. These different interaction modes are b riefly discussed, with particular emphasis on the interaction between matri x metalloproteinases (MMPs) and their endogenous tissue inhibitors of metal loproteinases (TIMPs).