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 ORCID: (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

[thumbnail of Accepted manuscript]
PDF (Accepted manuscript) - Accepted Version
Download (1MB) | Preview


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 tetranitrosyl [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
Uncontrolled Keywords: gene regulation,mass spectrometry,nitric oxide,sulfur,catalysis,organic chemistry ,/dk/atira/pure/subjectarea/asjc/1500/1503
Faculty \ School: Faculty of Science > School of Chemistry
UEA Research Groups: Faculty of Science > Research Centres > Centre for Molecular and Structural Biochemistry
Faculty of Science > Research Groups > Chemistry of Life Processes
Related URLs:
Depositing User: LivePure Connector
Date Deposited: 14 Dec 2018 14:30
Last Modified: 21 Oct 2022 21:31
DOI: 10.1002/chem.201806113


Downloads per month over past year

Actions (login required)

View Item View Item