Institut de Biologie StructuraleGrenoble / France

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

Metalloproteins Unit - Structure/Function Relationships

Group Leader : 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 signal-sensing function of FeS clusters (O2, NO, …) to regulate gene transcription. Another 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, CEA Researcher)
  • Patricia Amara (CEA Researcher)
  • Mickaël Cherrier (UGA Assistant Professor)
  • Eugenio de la Mora (CEA Researcher)
  • Eve de Rosny (UGA Assistant Professor)
  • Juan Fontecilla-Camps (Head from 1992 to 2015, CEA Research Director until 2021, now CEA Scientific Advisor)
  • Emilie Launay (PhD student)
  • Lydie Martin (CEA Engineer)
  • Tu Quynh Nguyen (PhD Student)
  • Juneina Omeiri (PhD Student)
  • Lucia Paya Tormo (Collaborator)
  • Jérémie Ruel (2021 : PhD Student, Master 2 student)
  • Anthony Usclat (Technician)
  • Xavier Vernède (CEA Engineer)
  • Anne Volbeda (CEA Researcher)


  • Amandine Barbaroux (L3 student)
  • Nkene Owone Olivia (Master 1 student)
  • Roman Rohac (Post-doctoral fellow)
  • Leon Jenner (Post-doctoral fellow)
  • Julie Michelon (L2 student)
  • Noëlie Palermo (L3 student)
  • Maelys Baudin (BTS trainee)
  • Fanny Lanoé (Master 1 student)
  • Ti-My Phuong Do (Master 2 student)
  • Rania Khouja (L3 student)
  • Mathias Eymery (Master 2 student)
  • Raleb Taher (PhD Student)
  • Maxime Bella (PhD Student)
  • Adriano Lopes Rodrigues (Master 2 student)
  • Anh Nguyen (Master 2 student)
  • Mathieu Viennois (L3 student)
  • 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)
  • Mélanie Rodà (L1 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

  • Fabien Chenavier (Technician)
  • David Fernandez-Remolar (Visiting Scientist)
  • Claire Saragaglia (Technician)
  • Ana Sosa Fajardo (Assistant Engineer)
  • Clara Rinaldi (Technician)
  • Claudine Darnault (CEA Technician)
  • Océane Gigarel (Technician)
  • Lucia Paya Tormo (Visiting PhD Student)
  • Viviam Moura da Silva (Visiting PhD Student)
  • Oriane Renoux (Technician)
  • Mónica Navarro Rodriguez (Visiting PhD Student)
  • Laura Zeppieri (Technician)
  • Myriam Savard (Technician)

Research topics

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

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, Martin L, Liu L, Basu D, Tao L, Britt RD, Rauchfuss TB, Nicolet Y (2021) Crystal Structure of the [FeFe]-Hydrogenase Maturase HydE Bound to Complex-B. Journal of the American Chemical Society 143 : 8499-8508.
  • Sosa Fajardo A, Legrand P, Payá-Tormo L, Martin L, Pellicer Martinez MT, Echavarri-Erasun C, Vernède X, Rubio L, Nicolet Y (2020) Structural insights into the mechanism of the radical SAM carbide synthase NifB, a key nitrogenase cofactor maturating enzyme 142 : 11006-11012.
  • Crack JC, Amara P, Volbeda A, Mouesca JM, Rohac R, Pellicer Martinez MT, Huang CY, Gigarel O, Rinaldi C, Le Brun NE and Fontecilla-Camps JC (2020) Electron and proton transfers modulate DNA binding by the transcription regulator RsrR. Journal of the American Chemical Society 142:5104-5116.
  • Amara P, Mouesca JM, Bella M, Martin L, Saragaglia C, Gambarelli S and Nicolet Y (2018) Radical S-adenosyl-L-methionine tryptophan lyase (NosL) : how the protein controls the carboxyl radical °CO2- migration. Journal of the American Chemical Society 140 : 16661-16668.
  • Volbeda A, Dodd EL, Darnault C, Crack JC, Renoux O, Hutchings MI, Le Brun NE and Fontecilla-Camps JC (2017) Crystal structures of the NO sensor NsrR reveal how its iron-sulfur cluster modulates DNA binding. Nature Communications 8:15052.
  • 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.

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