Characterization of A Stable Intermediate Trapped during Reversible Refolding of Bacillus Subtilisα‐Amylase

Abstract
Bacillus subtilis exocellular α‐amylase is reversibly refolded after denaturation by guanidine hydrochloride at pH 7 and 370C. The unfolding‐folding transition monitored by intrinsic fluorescence changes and resistance to proteolysis was resolved into a two‐state transition. The first step (t1/2 < 1 s) led from D. the totally unfolded state, to C. a stable partially structured state of the protein. This folding intermediate was devoid of any enzyme activity and partially resistant to protease degradation. Calcium was required for the transition from C to N. the native state. This metal did not remain associated with the native form and could be replaced by barium or strontium, but not by magnesium. We discuss the hypothesis that C. the folding intermediate whose further transformation is under kinetic control, is the competent state involved in the secretion process of α‐amylase.