Conformation of a stable intermediate on the folding pathway of Staphylococcus aureus penicillinase.

The partly unfolded intermediate (state H) of penicillinase from Staphylococcus aureus PC1 is stable in 0.8 M guanidinium chloride at pH 7.0. It has been characterized by measurements of intrinsic viscosity, sedimentation and diffusion coefficients, leading to an equivalent hydrodynamic volume of five times that of the native penicillinase molecule. Values of alpha-helix content calculated from circular dichroism were 27% for penicillinase and 16% for state H. A multi-domain model is proposed for penicillinase in which the domains can separate without appreciable change in secondary structure. This model is important in understanding the means by which the enzyme activity can be controlled, and corresponds to a kinetic pathway of folding.