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Relating protein motion to catalysis
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This is an extensive review of experimental and theoretical evidence supporting the interplay between conformational dynamics of enzymes and their catalytic activities, with focus on two enzymes, dehydrofolate reductase and liver alcohol dehydrogenase .A network of coupled motions involving both fast thermal vibrations and low frequency modes is pointed out to modulate the interactions between enzyme, substrate and cofactor at the active site, facilitating the hydride transfer reaction.
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Hammes-Schiffer S., and Benkovic S.J. Relating protein motion to catalysis. Annu Rev Biochem 75 (2006) 519-541. This is an extensive review of experimental and theoretical evidence supporting the interplay between conformational dynamics of enzymes and their catalytic activities, with focus on two enzymes, dehydrofolate reductase and liver alcohol dehydrogenase .A network of coupled motions involving both fast thermal vibrations and low frequency modes is pointed out to modulate the interactions between enzyme, substrate and cofactor at the active site, facilitating the hydride transfer reaction.
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Changeux J.P., and Edelstein SJ. Allosteric mechanisms of signal transduction. Science 308 (2005) 1424-1428. This is an insightful review of the progress made in the last forty years in understanding the allosteric mechanisms of signal tranduction. The basic concepts underlying the MWC model are summarized, such as the pre-disposition of symmetric oligomeric structures to undergo cooperative changes and the occurrence of reversible transitions, or spontaneous 'switches' between discrete conformations, accessible in the absence of ligand. The importance of binding ligands at strategic locations such as interfaces between subunits or along symmetry axes is emphasized.
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Binding of ligands to the antibody SPE7 was analyzed using kinetic measurements and X-ray crystallography to show that small ligands bind using the SPE7 pre-existing equilibrium followed by an induced fit that produces a high affinity complex. Nonspecific ligands are also able to bind the antibody. However, they are unable to induce the conformational changes for optimizing their interaction with SPE7, and consequently dissociate from the antibody.
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