Mass spectrometric identification of [4Fe-4S](NO)x intermediates of nitric oxide sensing by regulatory iron-sulfur cluster proteins

Crack, Jason C. and Le Brun, Nicolas (2019) Mass spectrometric identification of [4Fe-4S](NO)x intermediates of nitric oxide sensing by regulatory iron-sulfur cluster proteins. Chemistry - A European Journal, 25 (14). pp. 3675-3684. ISSN 0947-6539

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    Abstract

    Nitric oxide (NO) can function as both a cytotoxin and a signalling molecule. In both cases, reaction with iron‐sulfur (Fe‐S) cluster proteins plays an important role because Fe‐S clusters are reactive towards NO and so are a primary site of general NO‐induced damage (toxicity). This sensitivity to nitrosylation is harnessed in the growing group of regulatory proteins that function in sensing of NO via an Fe‐S cluster. Although information about the products of cluster nitrosylation is now emerging, detection and identification of intermediates remains a major challenge, due to their transient nature and the difficulty in distinguishing spectroscopically similar iron‐NO species. Here we report studies of the NO‐sensing Fe‐S cluster regulators NsrR and WhiD using non‐denaturing mass spectrometry, in which non‐covalent interactions between the protein and Fe/S/NO species are preserved. The data provide remarkable insight into the nitrosylation reactions, permitting identification, for the first time, of protein‐bound mono‐, di‐ and tetra‐nitrosyl [4Fe‐4S] cluster complexes ([4Fe‐4S](NO), [4Fe‐4S])(NO)₂ and [4Fe‐4S](NO)₄) as intermediates along pathways to formation of product Roussin’s red ester (RRE) and Roussin’s black salt (RBS)‐like species. The data allow the nitrosylation mechanisms of NsrR and WhiD to be elucidated and clearly distinguished.

    Item Type: Article
    Faculty \ School: Faculty of Science > School of Chemistry
    Depositing User: LivePure Connector
    Date Deposited: 14 Dec 2018 14:30
    Last Modified: 09 Apr 2019 14:00
    URI: https://ueaeprints.uea.ac.uk/id/eprint/69316
    DOI: 10.1002/chem.201806113

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