Interplay of structural preorganization and conformational sampling in UDP-glucuronic acid 4-epimerase catalysis.

ABSTRACT: Understanding enzyme catalysis as connected to protein motions is a major challenge. Here, based on temperature kinetic studies combined with isotope effect measurements, we obtain energetic description of C-H activation in NAD-dependent UDP-glucuronic acid C4 epimerase. Approach from the ensemble-averaged ground state (GS) to the transition state-like reactive conformation (TSRC) involves, alongside uptake of heat ( Δ H ‡  = 54 kJ mol^-1), significant loss in entropy ( - T Δ S ‡  = 20 kJ mol^-1; 298 K) and negative activation heat capacity ( Δ C p ‡  = -0.64 kJ mol^-1 K^-1). Thermodynamic changes suggest the requirement for restricting configurational freedom at the GS to populate the TSRC. Enzyme variants affecting the electrostatic GS preo

SUBMITTER: Rapp C 

PROVIDER: S-EPMC11519531 | biostudies-literature | 2024 May

REPOSITORIES: biostudies-literature