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Updated: Mar 7, 2026

Unraveling Entropic Rate Acceleration Induced by Solvent Dynamics in Membrane Enzymes
Published on: January 16, 2016
Combining multi-mutant and modular thermodynamic cycles to measure energetic coupling networks in enzyme catalysis
Charles W Carter1, Srinivas Niranj Chandrasekaran1, Violetta Weinreb1
1Department of Biochemistry and Biophysics, University of North Carolina at Chapel Hill , Chapel Hill, North Carolina 27599-7260, USA.
Abstract:
We measured and cross-validated the energetics of networks in Bacillus stearothermophilus Tryptophanyl-tRNA synthetase (TrpRS) using both multi-mutant and modular thermodynamic cycles. Multi-dimensional combinatorial mutagenesis showed that four side chains from this "molecular switch" move coordinately with the active-site Mg2+ ion as the active site preorganizes to stabilize the transition state for amino acid activation. A modular thermodynamic cycle consisting of full-length TrpRS, its Urzyme, and the Urzyme plus each of the two domains deleted in the Urzyme gives similar energetics. These dynamic linkages, although unlikely to stabilize the transition-state directly, consign the active-site preorganization to domain motion, assuring coupled vectorial behavior.
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