Crack, J.C. orcid.org/0000-0002-4979-1910, Amara, P. orcid.org/0000-0001-9634-7305, de Rosny, E. orcid.org/0000-0002-8197-8961 et al. (6 more authors) (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). 450. ISSN 2304-6740
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.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
Keywords: | FNR; gene regulation; nitric oxide sensing; iron–sulfur; molecular dynamics |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Science (Sheffield) > School of Biosciences (Sheffield) |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 12 Dec 2023 14:49 |
Last Modified: | 12 Dec 2023 14:49 |
Status: | Published |
Publisher: | MDPI AG |
Identification Number: | 10.3390/inorganics11120450 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:206464 |