Protein motions and dynamic effects in enzyme catalysis

• Published in: Physical chemistry chemical physics : PCCP Vol. 17; no. 46; pp. 3817 - 3827
• Main Authors: Luk, Louis Y. P, Loveridge, E. Joel, Allemann, Rudolf K
• Format: Journal Article
• Language: English
• Published: England 01.01.2015
• Subjects: Biocatalysis; Catalysis; Catalysts; Catalytic Domain; Coupling; Dynamics; Enzymes; Escherichia coli - enzymology; Escherichia coli - metabolism; Escherichia coli Proteins - chemistry; Escherichia coli Proteins - genetics; Escherichia coli Proteins - metabolism; Evolution; Kinetics; Mutagenesis, Site-Directed; Proteins; Solvents - chemistry; Tetrahydrofolate Dehydrogenase - chemistry; Tetrahydrofolate Dehydrogenase - genetics; Tetrahydrofolate Dehydrogenase - metabolism; Tuning
• ISSN: 1463-9076; 1463-9084; 1463-9084
• DOI: 10.1039/c5cp00794a

The role of protein motions in promoting the chemical step of enzyme catalysed reactions remains a subject of considerable debate. Here, a unified view of the role of protein dynamics in dihydrofolate reductase catalysis is described. Recently the role of such motions has been investigated by characterising the biophysical properties of isotopically substituted enzymes through a combination of experimental and computational analyses. Together with previous work, these results suggest that dynamic coupling to the chemical coordinate is detrimental to catalysis and may have been selected against during DHFR evolution. The full catalytic power of Nature's catalysts appears to depend on finely tuning protein motions in each step of the catalytic cycle. While the full catalytic power of dihydrofolate reductase depends on finely tuning protein motions in each step of the catalytic cycle, dynamic coupling to the actual chemical step is detrimental to catalysis.