The molecular basis of the effect of temperature on enzyme activity

  • Daniel R
  • Peterson M
  • Danson M
 et al. 
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Experimental data show that the effect of temperature on enzymes cannot be adequately explained in terms of a two-state model based on increases in activity and denaturation. The Equilibrium Model provides a quantitative explanation of enzyme thermal behaviour under reaction conditions by introducing an inactive (but not denatured) intermediate in rapid equilibrium with the active form. The temperature midpoint (T-eq) of the rapid equilibration between the two forms is related to the growth temperature of the organism, and the enthalpy of the equilibrium (Delta H-eq) to its ability to function over various temperature ranges. In the present study, we show that the difference between the active and inactive forms is at the enzyme active site. The results reveal an apparently universal mechanism, independent of enzyme reaction or structure, based at or near, the active site, by which enzymes lose activity as temperature rises, as opposed to denaturation which is global. Results show that activity losses below T-eq may lead to significant errors in the determination of Delta G(cat)* made on the basis of the two-state ('Classical') model, and the measured k(cat) will then not be a true indication of an enzyme's catalytic power. Overall, the results provide a molecular rationale for observations that the active site tends to be more flexible than the enzyme as a whole, and that activity losses precede denaturation, and provide a general explanation in molecular terms for the effect of temperature on enzyme activity.

Author-supplied keywords

  • Equilibrium Model
  • adaptation
  • ak.1 protease
  • conformational-changes
  • creatine-kinase
  • enzyme
  • evolution
  • guanidine-hydrochloride
  • inactivation precedes
  • kinetics
  • parameters
  • site
  • stability
  • temperature
  • thermal-denaturation
  • thermostability

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  • R M Daniel

  • M E Peterson

  • M J Danson

  • N C Price

  • S M Kelly

  • C R Monk

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