Energy landscape along an enzymatic reaction trajectory: hinges or cracks?

Are the most dynamically flexible regions around the equilibrium structure of an enzyme the same regions involved in the transition state for rate limiting processes involved in the enzymatic reaction? Kern and-coworkers (Wolf-Watzet al., 2004; Henzler-Wildman et al., 2007a, 2007b) have shown that insights about functionally relevant motions that determine the overall enzyme turnover rate can be obtained by investigating conformational dynamics around the equilibrium basin of the enzyme adenylate kinase. An allosteric change in protein structure turns out to be the controlling process. In this commentary we compare results of this study with earlier predictions of the route by which the enzyme undergoes its conformational change. These predictions are based on the idea that the energy surface for the protein is determined by the end structures of the conformational change. A key issue is whether the protein moves by specific hinges or whether it "cracks" and accesses partially unfolded states during its structural change.