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Light‐activated electron transfer and catalytic mechanism of carnitine oxidation by Rieske‐type oxygenase from human microbiota

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Shanmugam, Muralidharan, Quareshy, Mussa, Cameron, Alexander, Bugg, Timothy D. H. and Chen, Yin (2020) Light‐activated electron transfer and catalytic mechanism of carnitine oxidation by Rieske‐type oxygenase from human microbiota. Angewandte Chemie International Edition . doi:10.1002/anie.202012381 (In Press)

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WRAP-light‐activated-electron-transfer-catalytic-mechanism-carnitine-oxidation-Rieske‐type-oxygenase-human-microbiota-Chen-2020.pdf - Accepted Version
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Official URL: https://doi.org/10.1002/anie.202012381

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Abstract

Multi‐component, non‐heme iron‐dependent oxygenases catalyse a range of biochemical processes, as extensive as those found in heme chemistry. Oxidation of quaternary ammonium substrate carnitine by Acinetobacter baumannii (Ab) oxygenase CntA/ reductase CntB is implicated in the onset of human cardiovascular disease. However, detailed mechanistic understanding of the CntAB reaction is not known. Here, we develop a blue‐light (365 nm) activation of NADH coupled to electron paramagnetic resonance (EPR) measurements to study electron transfer from the excited state of NADH to the oxidised, Rieske‐type, [2Fe‐2S] 2+ cluster in the AbCntA oxygenase domain with and without the substrate, carnitine. Further electron transfer from one‐electron reduced, Rieske‐type [2Fe‐2S] 1+ centre in AbCntA‐WT to the mono‐nuclear, non‐heme iron centre via the bridging glutamate E205 and subsequent catalysis occurs only in the presence of carnitine. The reaction mechanism for photoactivated, NADH‐driven carnitine oxidation is different from the reaction driven by the AbCntB reductase partner. The electron transfer process in the AbCntA‐E205A mutant is severely affected, which plausibly accounts for the significant loss of catalytic activity in the AbCntA‐E205A mutant. The NADH photo‐activation coupled with EPR is broadly applicable to trap reactive intermediates at low temperature and creates a new method to characterise elusive intermediates in multiple redox‐centre containing proteins.

Item Type: Journal Article
Subjects: Q Science > QC Physics
Q Science > QD Chemistry
Q Science > QP Physiology
Divisions: Faculty of Science > Chemistry
Faculty of Science > Life Sciences (2010- )
Library of Congress Subject Headings (LCSH): Oxygenases, Metalloenzymes, Catalysis, Charge exchange, Carnitine
Journal or Publication Title: Angewandte Chemie International Edition
Publisher: Wiley - V C H Verlag GmbH & Co. KGaA
ISSN: 1433-7851
Official Date: 12 November 2020
Dates:
DateEvent
12 November 2020Available
6 November 2020Accepted
Date of first compliant deposit: 16 November 2020
DOI: 10.1002/anie.202012381
Status: Peer Reviewed
Publication Status: In Press
Publisher Statement: This is the peer reviewed version of the following article: Shanmugam, M., Quareshy, M., Cameron, A., Bugg, T..D.H. and Chen, Y. (2020), Light‐Activated Electron Transfer and Catalytic Mechanism of Carnitine Oxidation by Rieske‐type Oxygenase from Human Microbiota. Angew. Chem. Int. Ed.. Accepted Author Manuscript., which has been published in final form at https://doi.org/10.1002/anie.202012381. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions.
Access rights to Published version: Open Access
RIOXX Funder/Project Grant:
Project/Grant IDRIOXX Funder NameFunder ID
RPG-2016-307Leverhulme Trusthttp://dx.doi.org/10.13039/501100000275

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