A5014783337- Ubiquitin and proteasome pathways
- Chemical Synthesis and Analysis
- X-ray Diffraction in Crystallography
- Crystallization and Solubility Studies
- Peptidase Inhibition and Analysis
- Glycosylation and Glycoproteins Research
- Click Chemistry and Applications
- Advanced Proteomics Techniques and Applications
- Advanced Fluorescence Microscopy Techniques
- Advanced Biosensing Techniques and Applications
- interferon and immune responses
- Protein Kinase Regulation and GTPase Signaling
- Cellular transport and secretion
- Crystallography and molecular interactions
- Epigenetics and DNA Methylation
- Hedgehog Signaling Pathway Studies
- Growth Hormone and Insulin-like Growth Factors
- Cancer-related gene regulation
- Metabolism, Diabetes, and Cancer
- Cell Image Analysis Techniques
- Receptor Mechanisms and Signaling
- Metabolomics and Mass Spectrometry Studies
- Heat shock proteins research
- Genomic variations and chromosomal abnormalities
- Connexins and lens biology
Université de Bordeaux
2024-2025
Centre National de la Recherche Scientifique
2014-2025
Chimie et Biologie des Membranes et des Nanoobjects
2025
Technologies pour la Santé
2025
Rockefeller University
2014-2024
Institut Européen de Chimie et Biologie
2024
Institut Polytechnique de Bordeaux
2024
Imperial College London
2011-2019
The Francis Crick Institute
2015-2018
Immunologie, Immunopathologie et Chimie Thérapeutique
2014
Protein N-myristoylation is a ubiquitous co- and post-translational modification that has been implicated in the development progression of range human diseases. Here, we report global N-myristoylated proteome cells determined using quantitative chemical proteomics combined with potent specific N-myristoyltransferase (NMT) inhibition. Global quantification during normal growth or apoptosis allowed identification >100 proteins, >95% which are identified for first time at endogenous levels....
Significance Cysteine fatty acylation (S-fatty acylation) regulates the stability, trafficking, and activity of proteins in eukaryotes. Current methods to study S-fatty rely on metabolic incorporation acid analogs or selective chemical labeling affinity purification, which limits detection endogenous acylated protein isoforms levels. Here we demonstrate that biochemical exchange acyl groups cysteines with defined mass-tags enables direct visualization The application this mass-tag method...
N-Myristoyltransferase (NMT) covalently attaches a C14 fatty acid to the N-terminal glycine of proteins and has been proposed as therapeutic target in cancer. We have recently shown that selective NMT inhibition leads dose-responsive loss N-myristoylation on more than 100 protein targets cells, cytotoxicity cancer cells. lies upstream multiple pro-proliferative oncogenic pathways, but date complex substrate specificity limited determination which diseases are most likely respond inhibitor....
S-Fatty-acylation is the covalent attachment of long chain fatty acids, predominately palmitate (C16:0, S-palmitoylation), to cysteine (Cys) residues via a thioester linkage on proteins. This post-translational and reversible lipid modification regulates protein function localization in eukaryotes important mammalian physiology human diseases. While chemical labeling methods have improved detection enrichment S-fatty-acylated proteins, mapping sites characterizing endogenously attached acids...
The covalent coupling of fatty acids to proteins provides an important mechanism regulation in cells. In eukaryotes, cysteine acylation (S-fatty acylation) has been shown be critical for protein function a variety cellular pathways as well microbial pathogenesis. While methods developed over the past decade have improved detection and profiling S-fatty acylation, these are hampered their ability characterize endogenous levels under physiological conditions. Furthermore, understanding...
Abstract Dietary unsaturated fatty acids, such as oleic acid, have been shown to be covalently incorporated into a small subset of proteins, but the generality and diversity this protein modification has not studied. We synthesized fatty‐acid chemical reporters determined their targets in mammalian cells. The can induce formation lipid droplets site‐specifically onto known fatty‐acylated proteins label many Quantitative proteomics analysis revealed that acids modify similar saturated...
Abstract Structural analysis of a co‐crystal helically‐folded peptide‐foldamer hybrid in complex with hDM2 E3 ubiquitin ligase, revealed unique orientation for the C ‐terminal proline pyrrolidine ring pointing backwards sequence, and suggested new opportunities macrocyclization. In particular, we found that prolyl residue could be replaced by its (2 S ,4 )‐4‐mercaptoprolyl analogue optimal bisthioether crosslinking cysteine installed at position 4 sequence. The resulting i , +7 stapled is...
Nanchangmycin is a natural product with broad-spectrum activity against various organisms, exhibiting antibiotic, antiviral, anticancer, and antifibrotic effects. belongs to the family of polyether ionophores proposed exert its therapeutic effects by altering ion gradients across biological membranes. Although this mechanism has been well characterised in cancer models, it does not fully explain how nanchangmycin inhibits Zika virus infection, as recently reported. The specific molecular...
Hedgehog signaling is critical for correct embryogenesis and tissue development. However, on maturation, also found to be aberrantly activated in many cancers. Palmitoylation of the secreted protein sonic hedgehog (Shh) by enzyme acyltransferase (Hhat) required functional signaling. To quantify this important posttranslational modification, vitro Shh palmitoylation assays employ radiolabeled fatty acids, which have limitations terms cost safety. Here we present a click chemistry armed...
Abstract Nearly isosteric oxo to thioxo substitution was employed interrogate the structure of foldamers with a urea backbone and explore relationship between helical folding hydrogen‐bonding interactions. A series oligomers bonds substituted by thiourea at discrete or all positions in sequence have been prepared their propensity studied using combination spectroscopic methods X‐ray diffraction. The outcome replacements on found depend whether central terminal ureas were modified. canonical...
BFSP1 (beaded filament structural protein 1, filensin) is a cytoskeletal expressed in the eye lens. It binds AQP0 vitro and its C-terminal sequences have been suggested to regulate water channel activity of AQP0. A myristoylated fragment from C-terminus was found enriched fractions. Here we identify as substrate for caspase-mediated cleavage at several sites including D433. Cleavage D433 exposes cryptic myristoylation sequence (434–440). We confirm that this an excellent both NMT1 2...
In this data article we describe synthetic and characterisation for four members of the 5-acyl-6,7-dihydrothieno[3,2-c]pyridine (termed "RU-SKI") class inhibitors Hedgehog acyltransferase, including associated NMR spectra final compounds. RU-SKI compounds were selected synthesis based on their published high potencies against enzyme target. 41 (9a), 43 (9b), 101 (9c), 201 (9d) profiled activity in related "Click chemistry armed linked immunosorbent assay to measure palmitoylation by...
We present an open source high content analysis instrument utilizing automated fluorescence lifetime imaging (FLIM) for assaying protein interactions using Förster resonance energy transfer (FRET) based readouts of fixed or live cells in multiwell plates. This provides a means to screen cell signaling processes read out intramolecular FRET biosensors intermolecular such as oligomerization heterodimerization, which can be used identify binding partners. describe here the functionality this...
An HCA-FLIM instrument is presented alongside exemplar oligomerisation, intermolecular and intramolecular FRET assays that require robust measurement of small lifetime changes.
Combining helical foldamers with α-peptides can produce α-helix mimetics a reduced peptide character and enhanced resistance to proteolysis. Previously, we engineered hybrid peptide-oligourea sequence replicating the N-terminal α-helical domain of p53 achieve high affinity binding hDM2. Here, further advance this strategy by combining foldamer approach side chain cross-linking create more constrained cell-permeable inhibitors capable effectively engaging target within cells. Starting from...
We present an open source high content analysis instrument utilizing automated fluorescence lifetime imaging (FLIM) for assaying protein interactions using Förster resonance energy transfer (FRET) based readouts of fixed or live cells in multiwell plates. This provides a means to screen cell signaling processes read out intramolecular FRET biosensors intermolecular such as oligomerization heterodimerization, which can be used identify binding partners. describe here the functionality this...