Kinetics and thermodynamics of ligand binding to a molten globular enzyme and its native counterpart.

Kinetics and thermodynamics of ligand binding to a molten globular enzyme and its native counterpart. Research Abstract Details 

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Kinetics and thermodynamics of ligand binding to a molten globular enzyme and its native counterpart. Abstract Text:

An engineered monomeric chorismate mutase (mMjCM) has been found to combine high catalytic activity with the characteristics of a molten globule. To gain insight into the dramatic structural changes that accompany binding of a transition-state analog, we examined mMjCM by isothermal calorimetry and compared it with its dimeric parent protein, MjCM (CM from Methanococcus jannaschii), a thermostable and conventionally folded enzyme. As expected for a ligand-induced ordering process, there is a large entropic penalty for binding to the monomer relative to the dimer (-TDeltaDeltaS=5.1+/-0.5 kcal/mol, at 20 degrees C). However, this unfavorable entropy term is largely offset by enthalpic gains (DeltaDeltaH=-3.5+/-0.4 kcal/mol), presumably arising from tightening of non-covalent interactions throughout the monomeric complex. Stopped-flow kinetic measurements further reveal that the catalytic molten globule binds and releases ligands significantly faster than its natural counterpart, demonstrating that partial structural disorder can speed up molecular recognition. These results illustrate how structural plasticity may strongly perturb the thermodynamics and kinetics of transition-state recognition while negligibly affecting catalytic efficiency.

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Kinetics and thermodynamics of ligand binding to a molten globular enzyme and its native counterpart. Journal Published:

PUBLICATION TYPE: Journal Article

Journal: Journal of molecular biology

VOLUME: 382

Page Numbers: 971-7

Journal Abbreviation: J. Mol. Biol.

ISSN: 1089-8638

DAY: 25

MONTH: 07

YEAR: 2008

Kinetics and thermodynamics of ligand binding to a molten globular enzyme and its native counterpart. Information

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LANGUAGE: eng

NlmUniqueID: 2985088

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Grant and Affiliation Information for Kinetics and thermodynamics of ligand binding to a molten globular enzyme and its native counterpart.

AFFILIATION: Laboratory of Organic Chemistry, ETH Zurich, Hönggerberg HCI F339, CH-8093 Zurich, Switzerland.

Country: England

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MEDLINETA: J Mol Biol

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