Linear Free Energy Relationships for Enzymatic Reactions: Fresh Insight from a Venerable Probe
John P. Richard, Judith R. Cristobal, Tina L. Amyes
Abstract
° determined by electron valence bond (EVB) calculations to model deprotonation of dihydroxyacetone phosphate (DHAP) in water and when bound to wild-type and variant forms of TIM to form the enediolate reaction intermediate. This correlation provides evidence that the stabilizing interactions of the transition state for TIM-catalyzed deprotonation of DHAP are optimized by placement of amino acid side chains in positions that provide for the maximum stabilization of the charged reaction intermediate, relative to the neutral substrate.
Topics & Concepts
ChemistryTransition stateStereochemistryCatalysisEnzyme catalysisSubstrate (aquarium)Enzyme kineticsCarbocationSubstituentTriosephosphate isomeraseAlkylEnzymeActive siteMedicinal chemistryOrganic chemistryOceanographyGeologyBiochemical and Molecular ResearchProtein Structure and DynamicsEnzyme Structure and Function