Over the last 15 years, we have invented precursors, developed new labeling protocols to introduce any combination of 13CH3-labeled amino acids into proteins produced in E. coli, and set up efficient assignment strategies. These combined lines of research, focused on methyl probes, allowed us to develop new NMR pulse sequences to :
(i) detect, for the first time in proteins, weak interactions such as unusual CH-π bonds involving aromatic side chains or peptidic-bonds ;
(ii) aquire high resolution NMR 2D spectra of a 0.5 MDa complex in less than 1 second ;
(iii) push the threshold for detection of distance constraints derived from inter-proton NOEs to 12 Å in large proteins.
Pushing the detection threshold of NOEs by one order of magnitude allowed us to separate key inter-chain information from the abundant intra-chain NOEs.
Key Publications
"Stereospecific Isotopic Labeling of Methyl Groups for NMR Studies of High Molecular Weight Proteins" Angewandte Chemie International Edition
"Direct Detection of CH/π Interactions in Proteins" Nature Chemistry
"Fast Two Dimensional NMR Spectroscopy of High Molecular Weight Protein Assemblies" Journal of American Chemical Society
"Methyl Specific Isotopic Labeling : A Molecular Tool Box for NMR Studies of Large Proteins" Current Opinion in Structural Biology
"Spectral editing of intra- and inter-chain methyl-methyl NOEs in protein complexes" Journal of Biomolecular NMR
"Site-Specific Introduction of Alanines for the NMR Investigation of Low-Complexity Regions and Large Biomolecular Assemblies" ACS Chemical Biology