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.

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.