Physical Organic Models for the Mechanism of Lysozyme Action

Dunn, Ben M.; Bruice, Thomas C.

doi:10.1002/9780470122822.ch1

Cited by 18 publications

(5 citation statements)

References 114 publications

(47 reference statements)

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“…However, here we would like to remind the reader of the preorganization effect. Early experiments with model compounds in solution which explored the role of electrostatic effects (by the use of charged groups in order to stabilize the TS charge distribution) came to the conclusion that such effects must necessarily be small190,191. Phenomenological attempts to estimate the magnitude of electrostatic contributions192 to catalysis reached similar conclusions.…”

Section: Enzyme Catalysis Is Due To Polar Preorganization But Thmentioning

confidence: 98%

At the dawn of the 21st century: Is dynamics the missing link for understanding enzyme catalysis?

2010

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Enzymes play a key role in almost all biological processes, accelerating a variety of metabolic reactions as well as controlling energy transduction, transcription and translation of genetic information, and signaling. They possess the remarkable capacity to accelerate reactions by many orders of magnitude compared to their uncatalyzed counterparts, making feasible crucial processes that would otherwise not occur on biologically relevant timescales. Thus, there is broad interest in understanding the catalytic power of enzymes on a molecular level. Several proposals have been put forward to try to explain this phenomenon, and one that has rapidly gained momentum in recent years is the idea that enzyme dynamics somehow contributes to catalysis. This review examines the dynamical proposal in a critical way considering basically all reasonable definitions, including (but not limited to) such proposed effects as "coupling between conformational and chemical motions", "landscape searches" and "entropy funnels". It is shown that none of these proposed effects have been experimentally demonstrated to contribute to catalysis, nor are they supported by consistent theoretical studies. On the other hand, it is clarified that careful simulation studies have excluded most (if not all) dynamical proposals. This review places significant emphasis on clarifying the role of logical definitions of different catalytic proposals, and on the need for a clear formulation in terms of the assumed potential surface and reaction coordinate. Finally, it is pointed out that electrostatic preorganization actually accounts for the observed catalytic effects of enzymes, through the corresponding changes in the activation free energies.

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Section: Enzyme Catalysis Is Due To Polar Preorganization But Thmentioning

confidence: 98%

At the dawn of the 21st century: Is dynamics the missing link for understanding enzyme catalysis?

2010

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“…That is, early experiments with model compounds in solution (e.g. refs and ) that explored the role of electrostatic effects (by introducing charged groups to stabilize the TS charge distribution, as illustrated schematically in Figure ) concluded that such effects must be small (e.g., see refs and ). Similarly, phenomenological attempts to estimate the magnitude of electrostatic contributions to catalysis 57 also indicated that such effects are small.…”

Section: Electrostatic Contributions Of Preorganized Active Sitesmentioning

confidence: 99%

Electrostatic Basis for Enzyme Catalysis

et al. 2006

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“…A careful study of the interaction between Asp-52 and Glu-35 in the active site of lysoayme (Thoma, 1974) has indicated that even in the interior of proteins electrostatic effects are too weak to provide a major catalytic advantage. Experiments with model compounds in water (Dunn and Bruice, 1973) have indicated that electrostatic effects cannot explain the catalytic power of enzymes. Early theoretical attempts to examine the field inside and around the protein using X-ray structures (Johannin and Kellersohn, 1972;Hayes and Kollman, 1976) suggested that the field inside proteins can be significant but these studies did not consider the induced dipoles of the protein and, more importantly, the solvent around it, that in most cases reduce electrostatic effects by a factor of 40!…”

Section: General Acid-base Catalysismentioning

confidence: 99%