Structural basis of the endoproteinase-protein inhibitor interaction.
Proteolytic enzymes are potentially hazardous to their protein environment, so that their activity must be carefully controlled. Living organisms use protein inhibitors as a major tool to regulate the proteolytic activity of proteinases. Most of the inhibitors for which 3D structures are available are directed towards serine proteinases, interacting with the active sites in a 'canonical' i.e. substrate-like manner via an exposed reactive site loop of conserved conformation. More recently, some non-canonically binding serine proteinase inhibitors directed against coagulation factors, in particular thrombin, a few cysteine proteinase inhibitors inhibitory towards papain-like proteinases, and three zinc endopeptidase inhibitors directed against metzincins and thermolysin have been characterised in the free and complexed state, displaying novel mechanisms of inhibition with their target proteinases. These different interaction modes are presented and briefly discussed with respect to the different strategies applied by nature.
Bode
W
W
Max-Planck-Institut für Biochemie, D-82152 Martinsried c/o, Munich, Germany. bode@biochem.mpg.de
Huber
R
R
D000818:Animals; D001665:Binding Sites; D055313:Cystatin B; D015891:Cystatins / Q000737:chemistry; D015853:Cysteine Proteinase Inhibitors / Q000737:chemistry; D010450:Endopeptidases / Q000737:chemistry*; D004791:Enzyme Inhibitors / Q000737:chemistry*; D006801:Humans; D019476:Insect Proteins / Q000737:chemistry; D020782:Matrix Metalloproteinases / Q000737:chemistry; D008958:Models, Molecular; D010206:Papain / Q000737:chemistry; D011487:Protein Conformation; D015842:Serine Proteinase Inhibitors / Q000737:chemistry; D013917:Thrombin / Q000037:antagonists & inhibitors / Q000737:chemistry; D019714:Tissue Inhibitor of Metalloproteinases / Q000737:chemistry
C524994:CSTB protein, human; D015891:Cystatins; D015853:Cysteine Proteinase Inhibitors; D004791:Enzyme Inhibitors; D019476:Insect Proteins; D015842:Serine Proteinase Inhibitors; D019714:Tissue Inhibitor of Metalloproteinases; C082506:rhodniin protein, Rhodnius; D055313:Cystatin B; D010450:Endopeptidases; D013917:Thrombin; D010206:Papain; D020782:Matrix Metalloproteinases