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Crack, Jason C., Amara, Patricia, de Rosny, Eve, Darnault, Claudine, Stapleton, Melanie R., Green, Jeffrey, Volbeda, Anne, Fontecilla-Camps, Juan C. and Le Brun, Nick E. 
ORCID: https://orcid.org/0000-0001-9780-4061
(2023)
Probing the reactivity of [4Fe-4S] fumarate and nitrate reduction (FNR) regulator with O2 and NO: Increased O2 resistance and relative specificity for NO of the [4Fe-4S] L28H FNR cluster.
Inorganics, 11 (12).
ISSN 2304-6740
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Abstract
The Escherichia coli fumarate and nitrate reduction (FNR) regulator acts as the cell’s master switch for the transition between anaerobic and aerobic respiration, controlling the expression of >300 genes in response to O2 availability. Oxygen is perceived through a reaction with FNR’s [4Fe-4S] cluster cofactor. In addition to its primary O2 signal, the FNR [4Fe-4S] cluster also reacts with nitric oxide (NO). In response to physiological concentrations of NO, FNR de-represses the transcription of hmp, which encodes a principal NO-detoxifying enzyme, and fails to activate the expression of the nitrate reductase (nar) operon, a significant source of endogenous cellular NO. Here, we show that the L28H variant of FNR, which is much less reactive towards O2 than wild-type FNR, remains highly reactive towards NO. A high resolution structure and molecular dynamics (MD) simulations of the closely related L28H-FNR from Aliivibrio fischeri revealed decreased conformational flexibility of the Cys20-Cys29 cluster-binding loop that is suggested to inhibit outer-sphere O2 reactivity, but only partially impair inner-sphere NO reactivity. Our data provide new insights into the mechanistic basis for how iron–sulfur cluster regulators can distinguish between O2 and NO.
| Item Type: | Article |
|---|---|
| Additional Information: | Funding Information: This work was supported by the Biotechnology and Biological Sciences Research Council (BBSRC) grant BB/V006851/1 (UK) and grant ANR-18-CE11-0010 from the Agence Nationale pour la Recherche (France). |
| Uncontrolled Keywords: | fnr,gene regulation,iron–sulfur,molecular dynamics,nitric oxide sensing,inorganic chemistry ,/dk/atira/pure/subjectarea/asjc/1600/1604 |
| Faculty \ School: | Faculty of Science > School of Chemistry (former - to 2024) |
| UEA Research Groups: | Faculty of Science > Research Groups > Chemistry of Life Processes Faculty of Science > Research Centres > Centre for Molecular and Structural Biochemistry |
| Related URLs: | |
| Depositing User: | LivePure Connector |
| Date Deposited: | 09 Dec 2023 01:39 |
| Last Modified: | 01 Oct 2024 01:56 |
| URI: | https://ueaeprints.uea.ac.uk/id/eprint/93924 |
| DOI: | 10.3390/inorganics11120450 |
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