Group leader: Solange Moréra This e-mail address is being protected from spambots. You need JavaScript enabled to view it

Theme

Our team is interested in elucidating action mechanisms of singles enzymes or within multi-molecular complexes. Our work allows supplying fundamental basis describing the enzyme’s molecular function. It will lead to the elaboration of new antimicrobial or new anticancerous agents (drug design) for our enzymes of interest which are considered as potential therapeutic targets. Our team possesses a strong expertise in structural analysis by crystallography of enzymatic mechanisms as the transfer of phosphate and sugar. We are also specialized in the study of protein-protein interactions, protein-DNA and protein-ligand interactions which are at the center of the biological processes we are interested in. Our main themes concern:

• Bacterial or viral proteins mainly involved in host-pathogen relationship.
• The molecular chaperon Hsp90 and its machinery through the study of inhibitor of Hsp90, target proteins of Hsp90 and finally the R2TP complex formed by two helicases and two co-chaperons of Hsp90.
• DNA modification or DNA repair enzymes using the base flipping mechanism

Experimental approach

We use protein crystallography to determine the 3D structure of proteins and analyze their function alone or within multimolecular assemblies. The structure-function analysis is completed by biochemical and biophysical studies in solution. Techniques usually used are:

• Production of proteins (cloning, mutagenesis, bacterial culture…)
• Purification of recombinant proteins (Chromatography of affinity, Gel filtration…)
• Enzymatic tests and inhibition measurement ( Spectrophotometry)
• Crystallization, X-rays crystallography and structural analysis
• Interactions determination (Microcalorimétrie, Fluorescence, BIAcore)
• Conformational analyses (Circular Dichroism, Ultracentrifugation, light scattering)
• Post-traductionnal modifications analysis (mass spectrometry)
• Bioinformatic and molecular modelisation

Current Collaborations

Atypical bacterial Tyrosine-kinases

• Christophe Grangeasse, IBCP, Lyon
• Ivan Mijakovic, Institut Micalis, Thiverval-Grignon
• Marie-Françoise Noirot-Gros, Institut Micalis, Jouy en Josas

Regulators of quorum-sensing chez B. cereus

• Didier Lereclus, GME, Guyancourt
• Josef Deutscher, MGM, Thiverval-Grignon

Effectors of T3SS from Salmonella- target human proteins

• Francisco Ramos-Morales, Dpt de génétique, Université de Séville, Espagne

Hsp90 machinery

• Marc Billaud, Institut Albert Bonniot, Grenoble
• Edouard Bertrand, IGM, Montpellier
• Christiane Branlant/Bruno Charpentier, MAEM, Nancy
• Sarah Sanglier, LSMBO, Strasbourg

Bacterial periplasmic proteins

• Denis Faure, ISV, Gif sur Yvette

DNA repair ou modification enzymes

• Murat Saparbaev, IGR, Villejuif
• Saulius Klimasauskas, Vilnius, Lituanie