Muscle acylphosphatase (AcP) is a small protein that folds very slowly
with two-state behavior. The conformational stability and the rates of folding
and unfolding have been determined for a number of mutants of AcP in order
to characterize the structure of the folding transition state. The results
show that the transition state is an expanded version of the native protein,
where most of the native interactions are partially established. The transition
state of AcP turns out to be remarkably similar in structure to that of the
activation domain of procarboxypeptidase A2 (ADA2h), a protein having the
same overall topology but sharing only 13% sequence identity with AcP. This
suggests that transition states are conserved between proteins with the same
native fold. Comparison of the rates of folding of AcP and four other proteins
with the same topology, including ADA2h, supports the concept that the average
distance in sequence between interacting residues (that is, the contact order)
is an important determinant of the rate of protein folding.
