doi: 10.1126/science.1130258.
The dynamic energy landscape of dihydrofolate reductase catalysis
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- PMID: 16973882
- DOI: 10.1126/science.1130258
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The dynamic energy landscape of dihydrofolate reductase catalysis
Science.
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Abstract
We used nuclear magnetic resonance relaxation dispersion to characterize higher energy conformational substates of Escherichia coli dihydrofolate reductase. Each intermediate in the catalytic cycle samples low-lying excited states whose conformations resemble the ground-state structures of preceding and following intermediates. Substrate and cofactor exchange occurs through these excited substates. The maximum hydride transfer and steady-state turnover rates are governed by the dynamics of transitions between ground and excited states of the intermediates. Thus, the modulation of the energy landscape by the bound ligands funnels the enzyme through its reaction cycle along a preferred kinetic path.
Comment in
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Structural biology. Dynamic visions of enzymatic reactions.Science. 2006 Sep 15;313(5793):1586-7. doi: 10.1126/science.1132851. Science. 2006. PMID: 16973868 No abstract available.
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