Dynamically Interacting Protein Networks Provide a Mechanism to Overcome the Enormous Intrinsic Barrier to Orotidine 5'-Monophosphate Decarboxylation.

ABSTRACT: Orotidine 5'-monophosphate decarboxylase (OMPDC) is among the most efficient enzymes known, accelerating the decarboxylation of the OMP by ∼17 orders of magnitude, primarily by lowering the enthalpy of activation by ∼28 kcal/mol. Despite this feature, OMPDC from Methanothermobacter thermautotrophicus requires ∼15 kcal/mol of activation energy following ES complex formation. This study applies temperature-dependent hydrogen-deuterium exchange mass spectrometry (TDHDX) to detect site-specific thermal protein networks that channel energy from solvent collisions to the active site. Comparative TDHDX of native OMPDC and a single-site variant (Leu123Ala) that alters the activation enthalpy for catalytic turnover reveals region-specific changes in protein flexibility, connecting local scaf

SUBMITTER: Dubey P 

PROVIDER: S-EPMC12395307 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature