Refining the reaction mechanism of O2 towards its substrate in cofactor-free dioxygenases
- Published
- Accepted
- Subject Areas
- Biochemistry
- Keywords
- computational chemistry, minimum-energy crossing point, oxygenase, density-functional theory, urate oxidase, glutamate decarboxylase, ring cleaving dioxygenase, DFT
- Copyright
- © 2016 Silva
- Licence
- This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, reproduction and adaptation in any medium and for any purpose provided that it is properly attributed. For attribution, the original author(s), title, publication source (PeerJ Preprints) and either DOI or URL of the article must be cited.
- Cite this article
- 2016. Refining the reaction mechanism of O2 towards its substrate in cofactor-free dioxygenases. PeerJ Preprints 4:e2145v1 https://doi.org/10.7287/peerj.preprints.2145v1
Abstract
Cofactor-less oxygenases perform challenging catalytic reactions between singlet substrates and triplet oxygen, in spite of apparently violating the spin-conservation rule. In bacterial ring-cleaving 2,4-dioxygenase, the active site has been suggested by quantum chemical computations to fine tune triplet oxygen reactivity, allowing it to interact rapidly with its singlet substrate without the need for spin inversion, and in urate oxidase the reaction is thought to proceed through electron transfer from the deprotonated substrate to an aminoacid sidechain, which then feeds the electron to the oxygen molecule. In this work, we perform additional quantum chemical computations on these two systems to elucidate several intriguing features unaddressed by previous workers. These computations establish that in both enzymes the reaction proceeds through direct electron transfer from substrate to O2 followed by radical recombination, instead of minimum-energy crossing points between singlet and triplet potential energy surfaces without formal electron transfer. The active site does not affect the reactivity of oxygen directly but is crucial for the generation of the deprotonated form of the substrates, which have redox potentials far below those of their protonated forms and therefore may transfer electrons to oxygen without sizeable thermodynamic barriers. This mechanism seems to be shared by most cofactor-less oxidases studied so far.
Author Comment
This is a submission to PeerJ for review.
Supplemental Information
Geometries
Cartesian coordinates of all intermediates optimized for the reaction mechanism of ring-cleaving oxygenase. The extracted file can be opened and visualized by most molecular viewer software.