Substrate activation for O2 reactions by oxidized metal centers in biology
- †Department of Chemistry, Stanford University, Stanford, CA 94305-5080; and
- ‡Department of Biochemistry, Molecular Biology and Biophysics and the Center for Metals in Biocatalysis, University of Minnesota, Minneapolis, MN 55455
-
Edited by Jack Halpern, University of Chicago, Chicago, IL, and approved September 21, 2007 (received for review June 22, 2007)
Abstract
The uncatalyzed reactions of O2 (S = 1) with organic substrates (S = 0) are thermodynamically favorable but kinetically slow because they are spin-forbidden and the one-electron reduction potential of O2 is unfavorable. In nature, many of these important O2 reactions are catalyzed by metalloenzymes. In the case of mononuclear non-heme iron enzymes, either FeII or FeIII can play the catalytic role in these spin-forbidden reactions. Whereas the ferrous enzymes activate O2 directly for reaction, the ferric enzymes activate the substrate for O2 attack. The enzyme–substrate complex of the ferric intradiol dioxygenases exhibits a low-energy catecholate to FeIII charge transfer transition that provides a mechanism by which both the Fe center and the catecholic substrate are activated for the reaction with O2. In this Perspective, we evaluate how the coupling between this experimentally observed charge transfer and the change in geometry and ligand field of the oxidized metal center along the reaction coordinate can overcome the spin-forbidden nature of the O2 reaction.
Footnotes
- §To whom correspondence should be addressed. E-mail: edward.solomon{at}stanford.edu
-
Author contributions: J.D.L. and E.I.S. designed research; and M.Y.M.P. and E.I.S. performed research, analyzed data, and wrote the paper.
-
The authors declare no conflict of interest.
-
This article is a PNAS Direct Submission.
- Abbreviations:
- LO,
- lipoxygenase;
- ES,
- enzyme–substrate;
- 3,4-PCD,
- protocatechuate 3,4-dioxygenase;
- PCA,
- protocatechuate;
- 5C,
- 5-coordinate;
- 6C,
- 6-coordinate;
- SOC,
- spin-orbit coupling.
- © 2007 by The National Academy of Sciences of the USA
