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Crack, Jason C., Gaskell, Alisa A., Green, Jeffrey, Cheesman, Myles R., Le Brun, Nick E. 
ORCID: https://orcid.org/0000-0001-9780-4061 and Thomson, Andrew J.
(2008)
Influence of the environment on the [4Fe−4S]2+ to [2Fe−2S]2+ cluster switch in the transcriptional regulator FNR.
Journal of the American Chemical Society, 130 (5).
pp. 1749-1758.
Abstract
In Escherichia coli, the switch between aerobic and anaerobic metabolism is primarily controlled by the fumarate and nitrate reduction transcriptional regulator FNR. In the absence of O2, FNR binds a [4Fe-4S]2+ cluster, generating a transcriptionally active dimeric form. Exposure to O2 results in the conversion of the cluster to a [2Fe-2S]2+ form, leading to dissociation of the protein into transcriptionally inactive monomers. The [4Fe-4S]2+ to [2Fe-2S]2+ cluster conversion proceeds in two steps. Step 1 involves the one-electron oxidation of the cluster, resulting in the release of Fe2+, generating a [3Fe-4S]1+ cluster intermediate, and a superoxide ion. In step 2, the cluster intermediate spontaneously rearranges to form the [2Fe-2S]2+ cluster, with the release of a Fe3+ ion and two sulfide ions. Here, we demonstrate that, in both native and reconstituted [4Fe-4S] FNR, the reaction environment and, in particular, the presence of Fe2+ and/or Fe3+ chelators can influence significantly the cluster conversion reaction. We demonstrate that while the rate of step 1 is largely insensitive to chelators, that of step 2 is significantly enhanced by both Fe2+ and Fe3+ chelators. We show that, for reactions in Fe3+-coordinating phosphate buffer, step 2 is enhanced to the extent that step 1 becomes the rate determining step and the [3Fe-4S]1+ intermediate is no longer detectable. Furthermore, Fe3+ released during this step is susceptible to reduction in the presence of Fe2+ chelators. This work, which may have significance for the in vivo FNR cluster conversion reaction in the cell cytoplasm, provides an explanation for apparently contradictory results reported from different laboratories.
| Item Type: | Article |
|---|---|
| Faculty \ School: | Faculty of Science > School of Chemistry (former - to 2024) |
| UEA Research Groups: | Faculty of Science > Research Groups > Chemistry of Light and Energy Faculty of Science > Research Groups > Chemistry of Life Processes Faculty of Science > Research Groups > Biophysical Chemistry (former - to 2017) Faculty of Science > Research Centres > Centre for Molecular and Structural Biochemistry Faculty of Science > Research Groups > Centre for Ocean and Atmospheric Sciences |
| Depositing User: | Rachel Smith |
| Date Deposited: | 29 Mar 2011 12:27 |
| Last Modified: | 24 Sep 2024 09:29 |
| URI: | https://ueaeprints.uea.ac.uk/id/eprint/27419 |
| DOI: | 10.1021/ja077455+ |
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