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Institut de Biologie StructuraleGrenoble / France

Contact person(s) related to this article / Nicolet Yvain

Metalloproteins Unit - Structure/Function Relationships

Responsable: Yvain Nicolet

Metals lie at the heart of chemical processes that are at the origin of life and they play a crucial role in the function of numerous important proteins. The specific properties of metals are used in catalytic processes that are often inaccessible for active sites lacking them. Conversely, the metal properties may be tuned by the protein environment in ways that are difficult to mimic in synthetic compounds. All these aspects are studied in the Metalloproteins Unit.

We use crystallographic and computational methods to study the function of metalloproteins, i.e. their catalytic mechanisms, substrate recognition, substrate/product diffusion pathways and their inhibition by molecules like O2. Several of the studied metalloenzymes are involved in the utilisation or production of gaseous compounds like H2, CO and CO2 (e.g. hydrogenases, CO dehydrogenase/acetyl-CoA synthase). We also study enzymes with an S-adenosylmethionine cofactor linked to a [4Fe-4S] cluster, which catalyze radical-based chemical reactions. Some of these are involved in the post-translational maturation of the metal-containing active sites of the already mentioned gas-processing metalloenzymes, which is crucial for their activity. Another important focus of our research consists of the study of metalloproteins functioning in FeS cluster biogenesis. More recently, we have become interested in proteins that use the oxygen-sensing function of FeS clusters to regulate gene transcription. Another recent activity is the design of artificial metalloenzymes. The majority of the investigated proteins are very sensitive to oxygen, necessitating their study under anaerobic conditions inside glove boxes.

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Team members

  • Yvain Nicolet (Head since January 2016, CEA Researcher)
  • Juan Fontecilla-Camps (Head from 1992 to 2015, CEA Research Director)
  • Patricia Amara (CEA Researcher)
  • Maxime Bella (PhD Student)
  • Mickaël Cherrier (UGA Assistant Professor)
  • Claudine Darnault (CEA Technician)
  • Eve De Rosny (UGA Assistant Professor)
  • Océane Gigarel (Technician)
  • Lydie Martin (CEA Engineer)
  • Viviam Moura da Silva (Visiting PhD Student)
  • Claire Saragaglia (Technician)
  • Ana Sosa Fajardo (Technician)
  • Raleb Taher (PhD Student)
  • Xavier Vernède (CEA Engineer)
  • Anne Volbeda (CEA Researcher)

Alumni

  • Chuchu Guo (L3 Student)
  • Camille Larosa (Master 1 Student)
  • Amélie Vessière (BTS trainee)
  • Roman Rohac (PhD Student)
  • Adrien Pagnier (PhD Student)
  • Pablo Rado (Master 2 Student)
  • Jade Reboulet (BTS trainee)
  • Karen Rihani (Master 2 Student)
  • Imen Khtatfi (Master 2 Student)
  • Mohamed Ben Amor (Master 1 Student)
  • Widade Ziani (PhD Student)
  • Elodie Marinoni (PhD Student)
  • Hugo Lebrette (PhD Student)

Former members since 2014

  • Oriane Renoux (Technician)
  • Mónica Navarro Rodriguez (Visiting PhD Student)
  • Laura Zeppieri (Technician)
  • Mélanie Rodà (L1 student)
  • Myriam Savard (Technician)

Research topics

  • Use of radical chemistry by S-adenosyl-L-methionine-dependent enzymes
  • Signal-sensing function of FeS clusters
  • Maturation of metal-clusters and metal-containing active sites
  • Biogenesis of FeS clusters
  • Protein FeS clusters involved in Lewis chemistry
  • Fundamental studies of hydrogenases and their oxygen sensitivity

Specialized techniques and available services


Manipulations under controlled atmospheres using glove boxes for anaerobic cell growth, protein purification, manual crystallization, automated crystallization, crystal manipulation and automated crystal visualization.

Selected recent publications

  • Rohac R, Amara P, Benjdia A, Martin L, Ruffié P, Favier A, Berteau O, Mouesca JM, Fontecilla-Camps JC and Nicolet Y (2016) Carbon–sulfur bond-forming reaction catalysed by the radical SAM enzyme HydE. Nature Chemistry 8(5): 491-500
  • Sicoli G, Mouesca JM, Zeppieri L, Amara P, Martin L, Barra AL, Fontecilla-Camps JC, Gambarelli S and Nicolet Y (2016) Fine-tuning of a radical-based reaction by radical S-adenosyl-L-methionine tryptophan lyase. Science 351: 1320-1323
  • Pagnier A, Martin L, Zeppieri L, Nicolet Y and Fontecilla-Camps JC (2016) CO and CN- syntheses by [FeFe]-hydrogenase maturase HydG are catalytically differentiated events. Proceedings of the National Academy of Sciences 113: 104-109
  • Volbeda A, Darnault C, Renoux O, Nicolet Y and Fontecilla-Camps JC (2015) The crystal structure of the global anaerobic transcriptional regulator FNR explains its extremely fine-tuned monomer-dimer equilibrium. Science Advances 1(11):e1501086
  • Nicolet Y, Zeppieri L, Amara P and Fontecilla-Camps JC (2014) Crystal Structure of Tryptophan Lyase (NosL): Evidence for Radical Formation at the Amino Group of Tryptophan. Angewandte Chemie International Edition 53(44): 11840-11844
  • Volbeda A, Darnault C, Parkin A, Sargent F, Armstrong FA and Fontecilla-Camps JC (2013) Crystal structure of the O2-tolerant membrane-bound hydrogenase 1 from Escherichia coli in complex with its cognate cytochrome b.
    Structure 21:184-90

A list of all publications since the year 2000 can be consulted here

A list of metalloprotein-related theses supervised by members and ex-members of the group can be consulted here