Jean-Marc Lancelin

Jean-Marc Lancelin
Claude Bernard University Lyon 1 | UCBL · Institut de Sciences Analytiques

Professor (CE2)

About

129
Publications
9,968
Reads
How we measure 'reads'
A 'read' is counted each time someone views a publication summary (such as the title, abstract, and list of authors), clicks on a figure, or views or downloads the full-text. Learn more
4,369
Citations
Introduction
Jean-Marc Lancelin currently works at the Institut de Sciences Analytiques, Claude Bernard University Lyon 1. Jean-Marc does research in Chemistry and Biochemistry. Their current project is 'Imaging inflammation in vivo in ischemic stroke: development of a multimodal NANOprobe & BRAIN imaging methods (NanoBrain)'.
Additional affiliations
May 2016 - October 2016
Claude Bernard University Lyon 1
Position
  • Vice-president for research and doctoral studies
January 2007 - present
University of Lyon
Position
  • Managing Director
Description
  • The Doctoral School of Chemistry in Lyon, France covers the research activity of about 300 PhD students in 10 host research institution with 170 PhD supervisors. Web site at http://www.edchimie-lyon.fr
September 1995 - July 2015
Universidad de León
Position
  • Professor (Full)

Publications

Publications (129)
Poster
Full-text available
Functions of biological macromolecules in living cells are essentially based on their abilities to interact selectively with other molecules in their environment for signaling and catalysis. Human peroxiredoxin 5 (hPrx5), a thiol active peroxidase involved in peroxide signaling pathways in the cell was proposed to trigger the post-ischemic inflamma...
Article
Full-text available
Funnel-metadynamics is a kind of computational simulation used to enhance the sampling of protein-ligand binding events in solution. By characterizing the binding interaction events an estimated absolute binding free-energy can be calculated. NMR and funnel-metadynamics were used to evaluate the binding interaction of pyrocatechol derivatives (cate...
Article
Full-text available
One of the intrinsic properties of proteins is their capacity to interact selectively with other molecules in their environment inducing many chemical equilibria each differentiated by the mutual affinities of the components. A comprehensive understanding of these molecular binding processes at atomistic resolution requires formally the complete de...
Poster
A key feature that defines protein function in living cells is their capacity to interact dynamically and selectively with other molecules in their environment. Human peroxiredoxin 5 (PRDX5) is member of thiol-active peroxidases including the 6 human peroxiredoxins which catalyze hydroperoxides decomposition through a complex catalytic pathway invo...
Article
Muscle creatine kinase (MCK; EC 2.7.3.2) is a 86 kDa homodimer that belongs to the family of guanidino kinases. MCK has been intensively studied for several decades, but it is still not known why it is a dimer because this quaternary structure does not translate into obvious structural or functional advantages over the homologous monomeric arginine...
Article
a b s t r a c t To date, the signal transducing adaptor molecule 2 (STAM2) was shown to harbour two ubiquitin binding domains (UBDs) known as the VHS and UIM domains, while the SH3 domain of STAM2 was reported to interact with deubiquitinating enzymes (DUBs) like UBPY and AMSH. In the present study, NMR evidences the interaction of the STAM2 SH3 do...
Article
Full-text available
As the upstream component of the ESCRT (endosomal sorting complexes required for transport) machinery, the ESCRT-0 complex is responsible for directing ubiquitinated membrane proteins to the multivesicular body pathway. ESCRT-0 is formed by two subunits known as Hrs (hepatocyte growth factor-regulated substrate) and STAM (signal transducing adaptor...
Article
Fragment-based drug discovery has become a powerful method for the generation of drug leads against therapeutic targets. Beyond the identification of novel and effective starting points for drug design, fragments have emerged as reliable tools for assessing protein druggability and identifying protein hot spots. Here, we have examined fragments res...
Article
Full-text available
Programmed cell death (PCD) has a key role in defence and development of all multicellular organisms. In plants, there is a large gap in our knowledge of the molecular machinery involved at the various stages of PCD, especially the early steps. Here, we identify kiss of death (KOD) encoding a 25-amino-acid peptide that activates a PCD pathway in Ar...
Article
The VHS domain of the Stam2 protein is a ubiquitin binding domain involved in the recognition of ubiquitinated proteins committed to lysosomal degradation. Among all VHS domains, the VHS domain of Stam proteins is the strongest binder to monoubiqiuitin and exhibits preferences for K63-linked chains. In the present paper, we report the solution NMR...
Article
Photolysable caged ligands are used to investigate protein function and activity. Here, we investigate the binding properties of caged nucleotides and their photo released products to well established but evolutionary and structurally unrelated nucleotide-binding proteins, rabbit muscle creatine kinase (RMCK) and human annexin A6 (hAnxA6), using sa...
Article
Fragment-based drug design consists of identifying low-molecular weight compounds that weakly bind to a target macromolecule and will then be modified or linked to yield potent inhibitors. The specificity of these low-complexity and low-affinity molecules has rarely been discussed in the literature. To address this question, NMR spectroscopy was us...
Article
The stereocontrolled synthesis of tricyclic compounds through an efficient and highly regioselective 5-exo-trig palladium catalyzed biscyclization process is reported, starting from compounds 1. The 6-endo competing cyclization can also be the only pathway leading to trans-octahydrophenanthrene. In this finely balanced competition, it appcared that...
Data
Chemical shift perturbation of the 15N-HSQC spectrum of PRDX5 (80 µM) in absence (black contours) and presence of 1 mM fragment F012 (blue), F090 (red) and F082 (green). The residues that exhibit significant chemical shift perturbations are labeled according to their sequence-specific assignment. (1.08 MB TIF)
Data
Identification of the binding region of the fragments into the 3D structure of PRDX5 (1HD2 PDB entry). The four regions 1 to 4 described in the text are labeled. The chemical shift variations are mapped into the 3D structure of the protein and colored in magenta. Proline residues located near the highlighted region are colored in blue (no NMR data...
Data
Superposition of the F152 fragment docked structure (magenta) with the original X-ray structure for benzoate (yellow) complexed with PRDX5. The PRDX5 surface is colored according to the electrostatic potential (red for the negative region, blue for the positive surface and yellow for the cysteine residue). (2.94 MB TIF)
Data
Dose-response relationship of the inhibition of PRDX5 by F152. The estimated IC50 from this plot is 105+8.5 µM. (2.10 MB TIF)
Article
Full-text available
The search for protein ligands is a crucial step in the inhibitor design process. Fragment screening represents an interesting method to rapidly find lead molecules, as it enables the exploration of a larger portion of the chemical space with a smaller number of compounds as compared to screening based on drug-sized molecules. Moreover, fragment sc...
Article
Fragment-based drug design consists of screening low-molecular-weight compounds in order to identify low-affinity ligands that are then modified or linked to yield potent inhibitors. The method thus attempts to build bioactive molecules in a modular way and relies on the hypothesis that the fragment binding mode will be conserved upon elaboration o...
Article
(1)H DOSY NMR experiments were used to investigate the macrostructure of the asphaltenes of Maya, Athabasca, and Buzurgan feedstocks in toluene-d(s) a 20 degrees C. The influence of the concentration of asphaltenes oil their diffusion coefficients is presented for the three asphaltenes. A separation between two classes of aggregates-one diffusion q...
Article
Full-text available
NMR spectroscopy has been used to map the interaction domain on Escherichia coli thioredoxin for the thioredoxin- dependent 5′-adenylylsulfate reductase from Pseudomonas aeruginosa (PaAPR). Seventeen thioredoxin amino acids, all clustered around Cys-32 (the more surface-exposed of the two active-site cysteines), have been located at the PaAPR bindi...
Article
The mean molecular weight and particle size of asphaltene aggregates extracted from Buzurgan feedstock have been evaluated by measuring the diffusivity by means of (1)H diffusion-ordered spectroscopy (DOSY) nuclear magnetic resonance (NMR), This technique, recently applied in the petroleum industry, appeared as a key too] to investigate the behavio...
Article
Bovine testis hyaluronidase (btHyal) had been shown to have direct effects on cancer cells and to be a useful adjuvant in several medicines. Furthermore this enzyme had been found to be membrane-associated. Thus, in this work, the interactions between btHyal and membranes were analyzed by using lipid monolayers at the air-water interface as a biomi...
Article
Getting a better understanding of asphaltene is required to design new catalysts and to develop novel conversion processes but is still a challenge since these macromolecules are composed of thousands of polydisperse molecules. Thus, new analytical techniques need to be developed. 1H-DOSY (Diffusion Ordered SpectroscopY) NMR technique is a powerful...
Article
Experimental NMR diffusion measure on polymers and on globular proteins are presented. These results, complemented with results found in the literature, enable a general description of effective fractal dimension for objects such as small organic molecules, sugars, polymers, DNA, and proteins. Results are compared to computational simulations as we...
Article
Water sonolysis leads to the formation of hydroxyl radicals (OH*). Various techniques are used to detect the OH* production and thus to assess the level of ultrasound-mediated cavitation generated in vitro. In this study, we used terephthalic acid (TA) as an OH* trap. This method is based on the fluorescent properties of hydroxyterephthalic acid (H...
Article
Heavy crude oils are more and more of interest for the oil industry to meet the growing worldwide energy demand. Asphaltenes, which are the heaviest and least reactive molecules in crude oils, have received great attention over the last few decades, because they are responsible for many problems occurring during hydrotreatment and hydroconversion....
Article
Thioredoxins are ubiquitous small-molecular-weight proteins (typically 100–120 amino-acid residues) containing an extremely reactive disulphide bridge with a highly conserved sequence -Cys-Gly(Ala/Pro)-Pro-Cys-. In bacteria and animal cells, thioredoxins participate in multiple reactions which require reduction of disulphide bonds on selected targe...
Article
Iturins are a group of antifungal produced by Bacillus subtilis. All are cyclic lipopeptides with seven alpha-amino acids of configuration LDDLLDL and one beta-amino fatty acid. The bacillomycin L is a member of this family and its NMR structure was previously resolved using the sequence Asp-Tyr-Asn-Ser-Gln-Ser-Thr. In this work, we carefully exami...
Article
Using an in-house fragment NMR library, we identified a set of ligands that bind rabbit muscular creatine kinase, an enzyme involved in key ATP-dependent processes. The ligands docked to the crystal structures of creatine kinase indicated that a phenylfuroic acid could enter into a pocket adjacent to the nucleotide binding site. This fragment serve...
Article
The NMR structure of the cyclic lipopeptide surfactin from Bacillus subtilis was determined in sodium dodecyl sulfate (SDS) micellar solution. The two negatively charged side chains of surfactin form a polar head opposite to most hydrophobic side chains, accounting for its amphiphilic nature and its strong surfactant properties. Disorder was observ...
Article
Several HLA-DR alleles present the immunodominant HA(306-318) peptide of haemagglutinin of the influenza virus to T cells. NMR data of the peptide in various water solutions exclude any alpha-helix or turn conformations. Circular dichroism and Fourier transform infrared spectroscopies indicate an estimated beta-extended structure in water of 31% an...
Article
Full-text available
1-Cys peroxiredoxins (1-Cys Prxs) are antioxidant enzymes that catalyze the reduction of hydroperoxides into alcohols using a strictly conserved cysteine. 1-Cys B-Prxs, homologous to human PrxVI, were recently shown to be reactivated by glutathione S-transferase (GST) π via the formation of a GST-Prx heterodimer and Prx glutathionylation. In contra...
Article
Full-text available
1-Cys peroxiredoxins (1-Cys Prxs) are antioxidant enzymes that catalyze the reduction of hydroperoxides into alcohols using a strictly conserved cysteine. 1-Cys B-Prxs, homologous to human PrxVI, were recently shown to be reactivated by glutathione S-transferase (GST) π via the formation of a GST-Prx heterodimer and Prx glutathionylation. In contra...
Article
Full-text available
Peroxiredoxin systems in plants were demonstrated involved in crucial roles related to reactive oxygenated species (ROS) metabolism and the linked cell signalling to ROS. Peroxiredoxins function as peroxidasic systems that combine at least a reactivating reductant agent like thioredoxins, and sometimes glutaredoxins and glutathion. In the past thre...
Article
Full-text available
The interfacial properties of bovine testicular hyaluronidase were investigated by demonstrating the association of hyaluronidase activity with membranes prepared from bovine testis. Protein adsorption to the air/water interface was investigated using surface pressure-area isotherms. In whichever way the interfacial films were obtained (protein inj...
Article
Although polyene macrolides are efficient antifungal agents with fungicidal mode of action, their use in medical practice is problematic due to their low solubility and significant human toxicity. In an attempt to address the solubility problem, we have obtained two analogues of nystatin with hydroxy groups at positions C31 and C33 through manipula...
Chapter
In the chloroplasts of eukaryotic photosynthetic cells, ferredoxin and thioredoxin are linked in a redox cascade which activates several catalysts of the Calvin cycle by molecular reduction of selected disulfide bridges. These two redox constituents are also present in Chlamydomonas reinhardtii and their properties are described. Ferredoxin is a nu...
Article
Full-text available
Intracellular accumulation of triphosphorylated derivatives is essential for the cytotoxic activity of nucleoside analogues. Different mechanisms opposing this accumulation have been described. We have investigated the dephosphorylation of monophosphorylated fludarabine (F-ara-AMP) by the purified cytoplasmic 5'-nucleotidase cN-II using HPLC and NM...
Article
Full-text available
Thioredoxin f (TRXf) is a key factor in the redox regulation of chloroplastic carbon fixation enzymes, whereas glutathione is an important thiol buffer whose status is modulated by stress conditions. Here, we report specific glutathionylation of TRXf. A conserved cysteine is present in the TRXf primary sequence, in addition to its two active-site c...
Article
Full-text available
Glutaredoxins (Grx) represent a large family of glutathione (GSH)-dependent oxidoreductases that catalyse the reduction of disulfides or glutathione mixed disulfide. Grx domains from pathogenic bacteria and plant Grxs have been recently reported to target specific peroxiredoxins (Prxs). The specificity that triggers the interaction between Grx and...
Article
In many vertebrate tissues, cytosolic 5'-nucleotidase II (cN-II) either hydrolyses or phosphorylates a number of purine (monophosphorylated) nucleosides through a scheme common to the Haloacid Dehalogenase superfamily members. It possesses a pivotal role in purine cellular metabolism and it acts on anti-tumoural and antiviral nucleoside analogues,...
Article
Peroxiredoxins (Prxs) constitute a family of thiol peroxidases that reduce hydrogen peroxide, peroxinitrite, and hydroperoxides using a strictly conserved cysteine. Very abundant in all organisms, Prxs are produced as diverse isoforms characterized by different catalytic mechanisms and various thiol-containing reducing agents. The oligomeric state...
Article
Full-text available
The gram-positive bacterium Streptomyces noursei ATCC 11455 produces a complex mixture of polyene macrolides generally termed nystatins. Although the structures for nystatins A1 and A3 have been reported, the identities of other components of the nystatin complex remain obscure. Analyses of the culture extract from the S. noursei wild type revealed...
Article
Full-text available
Delta-conotoxin EVIA, from Conus ermineus, is a 32-residue polypeptide cross-linked by three disulfide bonds forming a four-loop framework. delta-Conotoxin EVIA is the first conotoxin known to inhibit sodium channel inactivation in neuronal membranes from amphibians and mammals (subtypes rNa(v)1.2a, rNa(v)1.3, and rNa(v)1.6), without affecting rat...
Article
NMR spectroscopy has evolved dramatically over the past 15 years, establishing a new, reliable methodology for studying biomacromolecules at atomic resolution. The three-dimensional structure and dynamics of a biomolecule or a biomolecular complex is only one of the main types of information available using NMR. The spectral assignment to the speci...
Article
Peroxiredoxins (Prx's) are a superfamily of thiol-specific antioxidant proteins present in all organisms and involved in the hydroperoxide detoxification of the cell. The catalytic cysteine of Prx's reduces hydroperoxides and is transformed into a transient sulfenic acid (Cys-SOH). At high hydroperoxide concentration, the sulfenic acid can be overo...
Article
Full-text available
The purpose of this work was to screen clinical isolates of actinomycetes producing nonpolyenic antifungals. This choice was made to limit the problem of rediscovery of well-known antifungal families, especially polyenic antifungals. One hundred and ten strains were tested, using two diffusion methods and two test media, against three yeast species...
Article
Reaction-induced infrared difference spectroscopy (RIDS) has been used to investigate the nature of interactions of human annexin A6 (ANXA6) with nucleotides. RIDS results for ANXA6, obtained after the photorelease of GTP-gamma-S, ATP, or P(i) from the respective caged compounds, were identical, suggesting that the interactions between the nucleoti...