Transition state stabilization by general acid catalysis, water expulsion, and enzyme reorganization in Medicago savita chalcone isomerase.

ABSTRACT: In aqueous solution, Medicago savita chalcone isomerase (CHI) enhances the reaction rate for the unimolecular rearrangement of chalcone (CHN) into flavanone by seven orders of magnitude. Conformations of CHN and their relative free energies in water and CHI were investigated by the thermodynamic perturbation method. In water, CHN adopts two conformations (I and II) with conformation I being higher in energy than conformation II by 3 kcal/mol. Only I can give rise to a near attack conformer (NAC) where the nucleophile O2' and the electrophile C9 are placed in proximity. In CHI, I binds less tightly than II by approximately 2 kcal/mol, resulting in the free energy for NAC formation being approximately 2 kcal/mol higher in the enzyme than in water. This unfavorable feature in the ground state

SUBMITTER: Hur S 

PROVIDER: S-EPMC365689 | biostudies-literature | 2004 Mar

REPOSITORIES: biostudies-literature