English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools annual

Global: Zendy Free Plan

Global: Zendy Tools monthly

Global: Zendy Plus monthly

4-Oxalocrotonate tautomerase enzyme (4-OT) catalyzes the isomerization of 2-oxo-4-hexenedioate to 2-oxo-3-hexenedioate. The chemical process involves two proton transfers, one from a carbon of the substrate to the nitrogen of Pro1 and another from this nitrogen atom to a different carbon of the substrate. In this paper the isomerization has been studied using the combined quantum mechanical and molecular mechanical method with a dual-level treatment of the quantum subsystem employing the MPW1BK density functional as the higher level. Exploration of the potential energy surface shows that the process is stepwise, with a stable intermediate state corresponding to the deprotonated substrate and a protonated proline. The rate constant of the overall process has been evaluated using ensemble-averaged variational transition state theory, including the quantized vibrational motion of a primary zone of active-site atoms and a transmission coefficient based on an ensemble of optimized reaction coordinates to account for recrossing trajectories and optimized multidimensional tunneling. The two proton-transfer steps have similar free energy barriers, but the transition state associated with the first proton transfer is found to be higher in energy. The calculations show that reaction progress is coupled to a conformational change of the substrate, so it is important that the simulation allows this flexibility. The coupled conformational change is promoted by changes in the electron distribution of the substrate that take place as the proton transfers occur.

Critical Role of Substrate Conformational Change in the Proton Transfer Process Catalyzed by 4-Oxalocrotonate Tautomerase