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Updated: Jun 25, 2026
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Steady-state, Pre-steady-state, and Single-turnover Kinetic Measurement for DNA Glycosylase Activity
Published on: August 19, 2013
Fluctuating enzyme and its biological functions: positive cooperativity without multiple states
The Journal of Physical Chemistry. B
|February 7, 2009
Summary
Enzymes can exhibit positive cooperativity, showing sigmoidal binding, due to substrate-induced reduction in conformational fluctuations. This occurs even without significant structural changes, impacting cellular enzyme dynamics and drug interactions.
Area of Science:
- Biochemistry
- Enzyme kinetics
- Molecular dynamics
Background:
- Monomeric enzymes with slow conformational fluctuations in unbound states exhibit positive cooperativity during steady-state turnover.
- This phenomenon, known as mnemonic or hysteretic enzymes, is linked to enzyme dynamics.
Discussion:
- Positive cooperativity can arise even in a single thermodynamic unbound (E) state if its fluctuation amplitude exceeds that of the enzyme-substrate complex (ES).
- This effect is contingent on comparable fluctuation timescales between E and ES states, even without a mean structural shift.
- Slow conformational fluctuations are a common feature across many enzymes.
Key Insights:
- Substrate binding that decreases conformational fluctuations can lead to sigmoidal enzyme kinetics.
- This mechanism explains cooperative binding in enzymes lacking significant structural transitions between unbound and bound states.
- The findings highlight the role of dynamic fluctuations in enzyme regulation.
Outlook:
- Sigmoidal binding kinetics may be more prevalent in cellular environments than previously thought.
- Understanding these dynamics can inform the design of drugs targeting enzyme activity.
- Further research into enzyme conformational dynamics could reveal new therapeutic strategies.
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