A Perspective on Enzyme Catalysis

@article{Benkovic2003APO,
  title={A Perspective on Enzyme Catalysis},
  author={Stephen J. Benkovic and Sharon Hammes-Schiffer},
  journal={Science},
  year={2003},
  volume={301},
  pages={1196 - 1202}
}
The seminal hypotheses proposed over the years for enzymatic catalysis are scrutinized. The historical record is explored from both biochemical and theoretical perspectives. Particular attention is given to the impact of molecular motions within the protein on the enzyme's catalytic properties. A case study for the enzyme dihydrofolate reductase provides evidence for coupled networks of predominantly conserved residues that influence the protein structure and motion. Such coupled networks have… 
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The utility of kinetic isotope effects (KIEs) and their temperature dependence as tools in probing such phenomena and the role of protein motions in their catalyzed reactions are discussed.
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TLDR
Experimental and theoretical evidence is presented to support the concept that enzyme mechanisms should be viewed as "catalytic networks" with multiple conformations that occur serially and in parallel in the mechanism.
Intrinsic dynamics of an enzyme underlies catalysis
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It is shown that the intrinsic plasticity of the protein is a key characteristic of catalysis, and the pre-existence of collective dynamics in enzymes before catalysis is a common feature of biocatalysts and that proteins have evolved under synergy pressure between structure and dynamics.
Structural bases of hydrogen tunneling in enzymes: progress and puzzles.
Origins of Enzyme Catalysis: Experimental Findings for C-H Activation, New Models, and Their Relevance to Prevailing Theoretical Constructs.
TLDR
A multidimensional model emerges that incorporates a range of protein motions that can be parsed into a combination of global stochastic conformational thermal fluctuations and local donor-acceptor distance sampling, and suggests a physical framework for understanding the empirical enthalpic barrier in enzyme-catalyzed processes.
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