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GREAM

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Breakthrough a glycyl radical enzyme long range activation mechanism

Glycyl radical enzymes (GREs) are one of the most prominent biological catalysts in both strict and facultative anaerobes. They are responsible for a broad range of radical-based chemistry and catalyse reactions involved in divers... ver más

02/06/2026

COLLEGE DE FRANCE

212K€

Presupuesto del proyecto: 212K€

Líder del proyecto

COLLEGE DE FRANCE No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

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Financiación concedida El organismo HORIZON EUROPE notifico la concesión del proyecto el día 2024-05-02

HORIZON-MSCA-2023-PF-01-01: MSCA Postdoctoral Fellowships 2023 ExpectedOutcome:Project results are expected to contribute to the following outcomes:

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2 Participantes

COLLEGE DE FRANCE

211.75K€ | Lider

LUNDS UNIVERSITET

N.D. | Participante

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Duración del proyecto: 25 meses Fecha Inicio: 2024-05-02
Fecha Fin: 2026-06-02

Líder del proyecto

COLLEGE DE FRANCE No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Presupuesto del proyecto 212K€

Descripción del proyecto Glycyl radical enzymes (GREs) are one of the most prominent biological catalysts in both strict and facultative anaerobes. They are responsible for a broad range of radical-based chemistry and catalyse reactions involved in diverse metabolic pathways such as acid fermentation, DNA synthesis and the anaerobic metabolism of pollutants. GREs are activated by members of the S-adenosylmethionine (SAM) radical family. Activation of GREs requires the formation of a protein-protein activation complex with the small GRE-AE. All known structures of GREs show that a major conformational change very likely occurs during the glycyl radical generation upon interaction with the GRE-AE. Only a structure of a GRE:AE holocomplex would shed light on the unprecedented conformational changes involved in GRE activation. Glycyl radicals and iron-sulfur clusters are extremely oxygen sensitive, rendering the proteins challenging to work with. GREAM will narrow a significant knowledge gap by studying the anaerobic class III RNR natural fusion (NrdD:NrdG). In order to study the mechanism of activation, GREAM will use an integrative research approach combining biochemical, biophysical and cryo-EM – assisted by X-ray crystallography. With my experience in anaerobic protein characterisation and crystallisation, I will join the Fontecave lab to build up on their experience in spectroscopic characterisation of oxygen-sensitive protein complexes and achieve the first aim or GREAM. During a secondment in the Logan lab, who are expert in structural characterisation of aRNRs and have a long lasting collaboration with the host, I will solve the anaerobic cryo-EM structure of the NrdD:NrdG holocomplex and achieve the final goal of GREAM. This newly established international collaboration will permit combining integrative approaches to successfully answer all GREAM’s questions and allow me to acquire invaluable experience in my future career.

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