Serpin-Protease Complexes Are Trapped as Stable Acyl-Enzyme Intermediates

摘要: The serine protease inhibitors of the serpin family are an unusual group proteins thought to have metastable native structures. Functionally, they unique among polypeptide inhibitors, although their precise mechanism action remains controversial. Conflicting results from previous studies suggested that stable serpin-protease complex is trapped in either a tight Michaelis-like structure, tetrahedral intermediate, or acyl-enzyme. In this report we show that, upon association with target protease, reactive-center loop (RCL) cleaved resulting formation acyl-enzyme intermediate. This cleavage coupled rapid movement RCL into body protein bringing inhibitor closer its lowest free energy state. From these data suggest model for which drive toward state trapping protease-inhibitor as