Histidine-assisted reduction of arylnitrenes upon photo-activation of phenyl azide chromophores in the GFP-like fluorescent proteins

Grigorenko, Bella L., Khrenova, Maria, Jones, D. Dafydd ORCID: https://orcid.org/0000-0001-7709-3995 and Nemukhin, Alexander 2024. Histidine-assisted reduction of arylnitrenes upon photo-activation of phenyl azide chromophores in the GFP-like fluorescent proteins. Organic and Biomolecular Chemistry 22 , pp. 337-347. 10.1039/D3OB01450A

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Abstract

The photochemically active sites of the proteins sfGFP66azF and Venus66azF from the green fluorescent protein (GFP) family contain a non-canonical amino acid residue p-azidophenylalanine (azF) instead of Tyr66 in GFP. Light-induced decomposition of azF in these sites leads to the reactive arylnitrene (nF) intermediates followed by formation of phenylamine-containing chromophores. We report the first study of a reaction mechanism of reduction of arylnitrene intermediates in sfGFP66nF and Venus66nF using molecular modeling methods. The Gibbs energy profiles for the elementary steps of chemical reaction in sfGFP66nF are computed using molecular dynamics simulations with the quantum mechanics/molecular mechanics (QM/MM) potentials. Structures and energies along the reaction pathway in Venus66nF are evaluated using the QM/MM approach. According to the results of simulations, arylnitrene reduction is coupled with oxidation of the histidine side chain His148 located near the chromophore.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Advanced Research Computing @ Cardiff (ARCCA) Biosciences
Publisher:	Royal Society of Chemistry
ISSN:	1477-0520
Date of First Compliant Deposit:	5 December 2023
Date of Acceptance:	20 November 2023
Last Modified:	20 Nov 2024 02:45
URI:	https://orca.cardiff.ac.uk/id/eprint/164539

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