A5068577689- Peptidase Inhibition and Analysis
- Nicotinic Acetylcholine Receptors Study
- Chemical Synthesis and Analysis
- RNA and protein synthesis mechanisms
- Monoclonal and Polyclonal Antibodies Research
- Microbial Natural Products and Biosynthesis
- Toxin Mechanisms and Immunotoxins
- Protease and Inhibitor Mechanisms
- Receptor Mechanisms and Signaling
- Signaling Pathways in Disease
- Biochemical and Structural Characterization
- Venomous Animal Envenomation and Studies
- Mass Spectrometry Techniques and Applications
- Antimicrobial Peptides and Activities
- Click Chemistry and Applications
- Ion channel regulation and function
- HIV Research and Treatment
- RNA modifications and cancer
- RNA Interference and Gene Delivery
- Immunotherapy and Immune Responses
- Insect and Pesticide Research
- Cell Adhesion Molecules Research
- Plant biochemistry and biosynthesis
- Radiopharmaceutical Chemistry and Applications
- DNA Repair Mechanisms
CEA Paris-Saclay
2011-2023
Commissariat à l'Énergie Atomique et aux Énergies Alternatives
2014-2023
Technologies pour la Santé
2020-2023
Université Paris-Saclay
2017-2023
Institut National de Recherche pour l'Agriculture, l'Alimentation et l'Environnement
2020-2023
Unité de Technologies Chimiques et Biologiques pour la Santé
2023
Institut de Biologie et Technologies
2008-2021
Centre d'Études Scientifiques et Techniques d'Aquitaine
2019-2021
Frédéric Joliot Institute for Life Sciences
2018
Bioénergétique et Ingénierie des Protéines
2009-2018
The gene encoding the cytochrome P450 CYP121 is essential for Mycobacterium tuberculosis. However, catalytic activity remains unknown. Here, we show that cyclodipeptide cyclo(l-Tyr-l-Tyr) (cYY) binds to CYP121, and efficiently converted into a single major product in assay containing spinach ferredoxin reductase. NMR spectroscopy analysis of reaction shows catalyzes formation an intramolecular C-C bond between 2 tyrosyl carbon atoms cYY resulting novel chemical entity. X-ray structure...
Microcin E492 (MccE492, 7886 Da), the 84-amino acid antimicrobial peptide from Klebsiella pneumoniae, was purified in a post-translationally modified form, MccE492m (8717 culture supernatants of either recombinant Escherichia coli VCS257 strain harboring pJAM229 plasmid or K. pneumoniae RYC492 strain. Chymotrypsin digestion led to MccE492m-(74–84) C-terminal fragment that carries modification and analyzed by mass spectrometry nuclear magnetic resonance at natural abundance. The 831-Da...
Cyclodipeptide synthases (CDPSs) use as substrates two amino acids activated aminoacyl-tRNAs to synthesize cyclodipeptides in secondary metabolites biosynthetic pathways. Since the first description of a CDPS 2002, number putative CDPSs databases has increased exponentially, reaching around 800 June 2017. They are likely be involved numerous pathways but diversity their products is still under-explored. Here, we describe activity 32 new CDPSs, bringing experimentally characterized about 100....
Cyclodipeptide synthases (CDPSs) belong to a newly defined family of enzymes that use aminoacyl-tRNAs (aa-tRNAs) as substrates synthesize the two peptide bonds various cyclodipeptides, which are precursors many natural products with noteworthy biological activities. Here, we describe crystal structure AlbC, CDPS from Streptomyces noursei. The AlbC consists monomer containing Rossmann-fold domain. Strikingly, it is highly similar catalytic domain class-I aminoacyl-tRNA synthetases (aaRSs),...
Disulfide-rich proteins or DRPs are versatile bioactive compounds that encompass a wide variety of pharmacological, therapeutic, and/or biotechnological applications. Still, the production in sufficient quantities is major bottleneck for their complete structural functional characterization. Recombinant expression such small containing multiple disulfide bonds bacteria E. coli considered difficult and general methods protocols, particularly on high throughput scale, limited. Here we report...
Barrier-to-autointegration factor (BAF), encoded by the BANF1 gene, is an abundant and ubiquitously expressed metazoan protein that has multiple functions during cell cycle. Through its ability to cross-bridge two double-stranded DNA (dsDNA), it favours chromosome compaction, participates in post-mitotic nuclear envelope reassembly essential for repair of large ruptures. BAF forms a ternary complex with proteins lamin A/C emerin, interaction defective patients recessive accelerated aging...
We investigated whether protein stability controls antigen presentation using a four disulfide-containing snake toxin and three derivatives carrying one or two mutations (L1A, L1A/H4Y, H4Y). These were anticipated to increase (H4Y) decrease (L1A) the non-covalent stabilizing interactions, H4Y being naturally frequently observed in neurotoxins. The chemically synthesized shared similar three-dimensional structure, biological activity, T epitope pattern. However, they displayed differential...
In Saccharomyces cerevisiae, double-strand breaks (DSBs) activate DNA checkpoint pathways that trigger several responses including a strong G(2)/M arrest. We have previously provided evidence the phosphatases Ptc2 and Ptc3 of protein phosphatase 2C type are required for inactivation after DSB probably dephosphorylate kinase Rad53. this article we investigated further interactions between showed forkhead-associated domain 1 (FHA1) Rad53 interacts with specific threonine Ptc2, T376, located...
Cytochrome P450 CYP121 is essential for the viability of Mycobacterium tuberculosis. Studies in vitro show that it can use cyclodipeptide cyclo(l-Tyr-l-Tyr) (cYY) as a substrate. We report an investigation substrate and reaction specificities involving analysis interaction between 14 cYY analogues with various modifications side chains or diketopiperazine (DKP) ring. Spectral titration experiments significantly bound only cyclodipeptides conserved DKP ring carrying two aryl l-configuration....
Copper-catalyzed and copper-free sydnone-alkyne cycloaddition reactions have emerged as complementary click tools for chemical biology but their use in bioorthogonal labeling is still its infancy. Herein, combinations of alkynes coumarin-sydnones were screened ability to generate pyrazole products displaying strong fluoroscence enhancement compared reactants. One sydnone was identified a particularly suitable new turn-on probe protein labeling.
Telomere integrity is essential to maintain genome stability, and telomeric dysfunctions are associated with cancer aging pathologies. In human, the shelterin complex binds TTAGGG DNA repeats provides capping chromosome ends. Within shelterin, RAP1 recruited through its interaction TRF2, TRF2 required for telomere protection a network of nucleic acid protein interactions. one most conserved proteins although unresolved question how may influence properties regulate capacity bind multiple...
Abstract We investigated venoms from members of the genus Atheris (Serpentes, Viperidae), namely rough scale bush viper ( squamigera ), green A. chlorechis ) and great lakes nitschei using mass spectrometry‐based strategies, relying on matrix‐assisted laser desorption/ionisation time‐of‐flight spectrometry (MALDI‐TOF‐MS) electrospray ionisation tandem (ESI‐MS/MS) with de novo peptide sequencing. discovered a set novel peptides masses in 2–3 kDa range containing poly‐His poly‐Gly segments...
Numerous food allergens of plant origin belong to the 2S albumin family, including peanut Ara h 2. In addition 2, several other conglutins related albumins are present in seeds. We evaluated allergenicity different as compared with Several were isolated from kernel, i.e. a new isoform 6 and its derived product, which is likely be naturally formed during seed processing. Enzyme allergosorbent tests performed on sera allergic patients showed that more than 94% 47 analyzed had positive IgE...
Venoms are a rich source of ligands for ion channels, but very little is known about their capacity to modulate G-protein coupled receptor (GPCR) activity. We developed strategy identify novel toxins targeting GPCRs.We studied the interactions mamba venom fractions with alpha(1)-adrenoceptors in binding experiments (3)H-prazosin. The active peptide (AdTx1) was sequenced by Edman degradation and mass spectrometry fragmentation. Its synthetic homologue pharmacologically characterized using...
BACKGROUND AND PURPOSE Muscarinic and adrenergic G protein‐coupled receptors (GPCRs) are the targets of rare peptide toxins isolated from snake or cone snail venoms. We used a screen to identify novel Dendroaspis angusticeps targeting aminergic GPCRs. These may offer new candidates for development tools drugs. EXPERIMENTAL APPROACH In binding experiments with 3 H‐rauwolscine, we studied interactions green mamba venom fractions α 2 ‐adrenoceptors rat brain synaptosomes. isolated, sequenced...
Abstract The manipulation of natural product biosynthetic pathways is a powerful means expanding the chemical diversity bioactive molecules. 2,5‐diketopiperazines (2,5‐DKPs) have been widely developed by medicinal chemists, but their biological production yet to be exploited. We introduce an in vivo method for incorporating non‐canonical amino acids (ncAAs) into 2,5‐DKPs using cyclodipeptide synthases (CDPSs), enzymes responsible scaffold assembly many 2,5‐DKP pathways. CDPSs use...
Weak neurotoxins from snake venom are small proteins with five disulfide bonds, which have been shown to be poor binders of nicotinic acetylcholine receptors. We report on the cloning and sequencing four cDNAs encoding weak Naja sputatrix glands. The protein encoded by one them, Wntx‐5, has synthesized solid‐phase synthesis characterized. physicochemical properties synthetic toxin (sWntx‐5) agree those anticipated for natural toxin. show that this interacts relatively low affinity ( K d =...
Mass spectroscopy, microsequencing, and site-directed mutagenesis studies have been performed to identify in human matrix metalloelastase (hMMP-12) residues covalently modified by a photoaffinity probe, previously shown be able label specifically the active site of metalloproteinases (MMPs). Results obtained led us conclude that photoactivation this probe complex with hMMP-12 affects single residue MMP-12, Lys(241), through covalent modification its side chain epsilon NH(2) group. Because...
CD4 binding on gp120 leads to the exposure of highly conserved regions recognized by HIV co-receptor CCR5 and CD4-induced (CD4i) antibodies. A covalent gp120-CD4 complex was shown elicit CD4i antibody responses in monkeys, which correlated with control virus infection (DeVico, A., Fouts, T., Lewis, G. K., Gallo, R. C., Godfrey, Charurat, M., Harris, I., Galmin, L., Pal, (2007) Proc. Natl. Acad. Sci. U.S.A. 104, 17477–17482). Because inclusion a vaccine formulation should be avoided, due...
Abstract MMP ‐11 is a key factor in physiopathological tissue remodeling. As an active form secreted, its activity must be tightly regulated to avoid detrimental effects. Although TIMP ‐1 and ‐2 reversibly inhibit ‐11, another more drastic scenario, presumably via hydrolysis, could hypothesized. In this context, we have investigated the possible implication of ‐14, since it exhibits spatiotemporal localization similar ‐11. Using native HFL 1‐produced HT ‐1080‐produced ‐14 as well recombinant...