Different reaction mechanisms for mesophilic and thermophilic dihydrofolate reductases.

@article{Loveridge2009DifferentRM,
  title={Different reaction mechanisms for mesophilic and thermophilic dihydrofolate reductases.},
  author={E Joel Loveridge and Enas M. Behiry and Richard S Swanwick and Rudolf K Allemann},
  journal={Journal of the American Chemical Society},
  year={2009},
  volume={131 20},
  pages={6926-7}
}
We report here solvent kinetic isotope effects for two dihydrofolate reductases, namely the monomeric, mesophilic enzyme from E. coli (EcDHFR) and the dimeric, thermophilic enzyme from Thermotoga maritima (TmDHFR). Multiple isotope effects reveal mechanistic differences between the two enzymes. EcDHFR follows a stepwise mechanism in which proton transfer precedes hydride transfer, whereas the two steps are concerted in TmDHFR. At elevated pH, EcDHFR also follows a concerted reaction pathway… CONTINUE READING

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