A reversible unfolding reaction of swine pepsin; implications for pepsinogen's folding mechanism

Above pH 6, swine pepsin undergoes a conformational change to a neutral form which has 80% of the secondary structure of the native protein. In contrast to native pepsin, this form of the enzyme can be reversibly unfolded by urea in a rapid, cooperative reaction. Since all of pepsin's sequence is present in its precursor pepsinogen, it is likely that this neutral structure is present in one or more of the transient intermediates previously detected in the reversible unfolding reaction of the zymogen. The mechanism of this rapid reaction may resemble early steps in protein folding.