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Curr Opin Chem Biol. 2010 Oct;14(5):636-43. doi: 10.1016/j.cbpa.2010.08.007. Epub 2010 Sep 6.

Choreographing an enzyme's dance.

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  • 1Department of Biochemistry, Howard Hughes Medical Institute, Brandeis University, 415 South St., Waltham, MA 02454, USA.

Abstract

While ground state structures combined with chemical tools and enzyme kinetics deliver useful information on possible chemical mechanisms of enzyme catalysis, they do not unravel the finely balanced energy inventory to explain the impressive rate enhancement of enzymes. For this goal, a complete description of enzyme catalysis in the form of an energy landscape is needed. Since the rate of catalysis is determined by the climb over a sequence of energy barriers, we focus here on the critical question of transition pathways. A combination of time-resolved NMR and simulation deliver a glimpse into how proteins can so efficiently move within the ensemble of the native conformations while avoiding unfolding during that journey. The loss of energy due to breakage of native contacts is compensated by non-native transient hydrogen bonds during the transition thereby 'holding on' to the energy until the new native contacts form that define the alternate functional state. The use of kinetic isotope effects (KIE) to study the chemical step show that coordinated atomic fluctuations of the protein component dictate the probability of 'correct' distance and orientation, due to its extreme sensitivity to distance. The examples here stress the point that highly choreographed conformational sampling together with chemical integrity is a prerequisite for efficient enzyme catalysis.

Copyright © 2010 Elsevier Ltd. All rights reserved.

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