The individual amide proton exchange rates in Tendamistat at pH 3.0 and 50 degrees C were measured by using two-dimensional 1H nuclear magnetic resonance. Overall, it was found that the distribution of exchange rates along the sequence is dominated by the interstrand hydrogen bonds of the beta-sheet structures. The slowly exchanging protons in the core of the two beta-sheets were shown to exchange via an EX2 mechanism. Further analysis of the data indicates that different large-scale structure fluctuations are responsible for the exchange from the two beta-sheets, even though the three-dimensional structure of Tendamistat appears to consist of a single structural domain.