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Abstract

BACKGROUND: Adenylate kinases undergo large conformational changes during their catalytic cycle. Because these changes have been studied by comparison of structures from different species, which share approximately one-third of their residues, only rough descriptions have been possible to date. RESULTS: We have solved the structure of unligated adenylate kinase from Escherichia coli at 2.2 degree resolution and compared it with the high-resolution structure of the same enzyme ligated with an inhibitor mimicking both substrates, ATP and AMP. This comparison shows that, upon substrate binding, the enzyme increases its chain mobility in a region remote from the active center. As this region 'solidifies' again on substrate release, we propose that it serves as a 'counterweight' balancing the substrate binding energy. CONCLUSION: The comparison of two very different conformations of the same polypeptide chain revealed kinematic details of the catalytic cycle. Moreover, it indicated that there exists an energetic counterweight compensating the substrate binding energy required for specificity. This counterweight prevents the enzyme from dropping into a rate-reducing energy well along the reaction coordinate.