A5056249534- Enzyme Structure and Function
- Plant biochemistry and biosynthesis
- Glycosylation and Glycoproteins Research
- Crystallization and Solubility Studies
- X-ray Diffraction in Crystallography
- Protein Structure and Dynamics
- Computational Drug Discovery Methods
- Monoclonal and Polyclonal Antibodies Research
- Microbial Natural Products and Biosynthesis
- Synthesis of Organic Compounds
- Carbohydrate Chemistry and Synthesis
- Hemoglobin structure and function
- Crystallography and molecular interactions
- Synthesis and biological activity
- Erythrocyte Function and Pathophysiology
- Legume Nitrogen Fixing Symbiosis
- Click Chemistry and Applications
- Analytical Chemistry and Chromatography
- Bacterial Infections and Vaccines
- Plant Gene Expression Analysis
- Photosynthetic Processes and Mechanisms
- Antifungal resistance and susceptibility
- Pharmacological Effects of Natural Compounds
- Protein Interaction Studies and Fluorescence Analysis
- DNA Repair Mechanisms
Université de Lille
2016-2024
Centre National de la Recherche Scientifique
2015-2024
Unité de Glycobiologie Structurale et Fonctionnelle
2015-2024
Institut National de Recherche pour l'Agriculture, l'Alimentation et l'Environnement
2022
Inserm
2010-2021
Centre Hospitalier Universitaire de Lille
2021
Danylo Halytsky Lviv National Medical University
2016
University of Namur
2004-2015
Université Lille Nord de France
2015
University of Utah
2008-2014
Abstract Blocking the adherence of bacteria to cells is an attractive complementary approach current antibiotic treatments, which are faced with increasing resistance. This strategy has been particularly studied in context urinary tract infections (UTIs), adhesion pathogenic Escherichia coli strains uroepithelial prevented by blocking FimH adhesin expressed at tips organelles called fimbriae. Recently, we extended antiadhesive concept, showing that potent antagonists can block attachment...
In this work, coumarins were screened on thrombin (THR) and factor Xa (FXa), two of the most promising targets for development anticoagulant drugs. This allowed us to highlight compound 30, characterized by a 2,5-dichlorophenyl ester in 3-position chloromethyl moiety 6-position, as very potent THR inhibitor (ki/KI = 37 000 M-1 s-1). Moreover, exhibits good selectivity over FXa (168-fold) trypsin (54-fold). The mechanism inactivation was investigated series significantly differs from that...
The origin and the nature of first hyperpolarizability collagen has been unraveled by performing first-principles calculations on PPG10 compound, a molecular model for triple helix structure, its building blocks. originates from amide groups. Owing to rigidity structure proline units, β-tensor components parallel helical axis add each other, whereas perpendicular cancel which result in dipolar depolarization ratio close 9. have also shown that resulting β values cannot be viewed as simple...
Abstract Background CD44 is a multifunctional membrane glycoprotein. Through its heparan sulfate chain, presents growth factors to their receptors. We have shown that and Tropomyosin kinase A (TrkA) form complex following nerve factor (NGF) induction. Our study aimed understand how TrkA interact the consequences of inhibiting this interaction regarding pro-tumoral effect NGF in breast cancer. Methods After determining which isoforms (variants) are involved forming TrkA/CD44 using proximity...
Emerging evidence indicates that the TRPM8 channel plays an important role in prostate cancer (PCa) progression, by impairing motility of these cells. Here, we reveal a novel facet PCa control via direct protein-protein interaction (PPI) with small GTPase Rap1A. The functional two proteins was assessed active Rap1 pull-down assays and live-cell imaging experiments. Molecular modeling analysis allowed identification four putative residues involved TRPM8-Rap1A interaction. Point mutations...
Abstract Non‐tuberculous mycobacterium (NTM) infections, such as those caused by Mycobacterium abscessus , are increasing globally. Due to their intrinsic drug resistance, M. pulmonary infections often difficult cure using standard chemotherapy. We previously demonstrated that a piperidinol derivative, named PIPD1, is an efficient molecule both against and tuberculosis the agent of tuberculosis, targeting mycolic acid transporter MmpL3. These results prompted us design synthesize series...
The N-terminal region is stabilized in the crystal structure of Thermus thermophilus type 2 isopentenyl diphosphate isomerase complex with inorganic pyrophosphate, providing new insights about active site and catalytic mechanism enzyme. PPi moiety located near conserved residues, H10, R97, H152, Q157, E158, W219, flavin cofactor. putative provides interactions for stabilizing a carbocationic intermediate similar to those that stabilize well-established protonation−deprotonation 1.
Selective inhibitors of the type 1 fimbrial adhesin FimH are recognized as attractive alternatives for antibiotic therapies and prophylaxes against Escherichia coli infections such urinary-tract infections. To construct these inhibitors, α-D-mannopyranoside high-mannose N -glycans, with exclusive specificity on glycoprotein receptors by FimH, forms basal structure. A hydrophobic aglycon is then linked to mannose O1 oxygen inherently present in α-anomeric configuration. Substitution this O...
Using the SIBFA polarizable molecular mechanics procedure, we analyze binding energy of a bimetallic Mg(II)/Zn(II) enzyme, isopentenyl diphosphate isomerase, to an inhibitor built up trianionic and cationic ethyldimethylammonium (EDMA) moiety. The analyses are performed on protein recognition site, which totals 13 residues, as well some "mutants" in one selected residue is removed at time. They also carried out for individual sites, namely, EDMA, Mg(II), Zn(II). Comparisons done with ab...
Abstract Thiazolylaminomannosides (TazMan) are FimH antagonists with anti‐adhesive potential against adherent‐invasive Escherichia coli (AIEC) promoting gut inflammation in patients Crohn's disease. The lead TazMan is highly potent vitro, but shows limited vivo efficiency, probably due to low pH stability and water solubility. We recently developed a second generation of stable TazMan, the effect was lower than first. Herein we report co‐crystal structure FimH, revealing that anomeric NH...
Abstract Protein structures inherently contain information that can be used to decipher their functions, but the exploitation of this knowledge is not trivial. We recently developed an app for Cytoscape network visualization and analysis program, called RINspector, goal which integrate two different approaches identify key residues in a protein structure or complex. The first approach consists calculating centralities on residue interaction (RIN) generated from three‐dimensional structure;...
The Sda carbohydrate epitope and its biosynthetic B4GALNT2 enzyme are expressed in the healthy colon down-regulated to variable extents cancer. human gene drives expression of a long short protein isoform (LF-B4GALNT2 SF-B4GALNT2) sharing identical transmembrane luminal domains. Both isoforms trans-Golgi proteins LF-B4GALNT2 also localizes post-Golgi vesicles thanks extended cytoplasmic tail. Control mechanisms underpinning gastrointestinal tract complex not fully understood. This study...
Candida albicans mannan consists of a large repertoire oligomannosides with different types mannose linkages and chain lengths, which act as individual epitopes more or less overlapping antibody specificities. Although anti-C. levels are monitored for diagnostic purposes nothing is known about the qualitative distribution these antibodies in terms epitope specificity. We addressed this question using bank previously synthesized biotin sulfone tagged (BSTOs) α β anomery complemented synthetic...
Isoprenoid compounds constitute an immensely diverse group of acyclic, monocyclic and polycyclic that play important roles in all living organisms. Despite the diversity their structures, this plethora natural products arises from only two 5-carbon precursors, isopentenyl diphosphate (IPP) dimethylallyl (DMAPP). This review will discuss enzymes mevalonate (MVA) methylerythritol phosphate (MEP) biosynthetic pathways leading to IPP DMAPP with a particular focus on MEP synthase (DXR) isomerase...
Topoisomerases are interesting targets in cancer chemotherapy. Here, we describe the design and synthesis of a novel copper(II) indenoisoquinoline complex, WN198. The new organometallic compound exhibits cytotoxic effect on five adenocarcinoma cell lines (MCF-7, MDA-MB-231, HeLa, HT-29, DU-145) with lowest IC50 (0.37 ± 0.04 μM) for triple-negative MDA-MB-231 breast line. Below 5 µM, WN198 was ineffective non-tumorigenic epithelial MCF-10A cells Xenopus oocyte G2/M transition or embryonic...
Abstract Isopentenyl diphosphate isomerase (IDI) is a key enzyme in the isoprenoid biosynthetic pathway and required for all organisms that synthesize metabolites from mevalonate. Type 1 IDI (IDI‐1) metalloprotein found eukaryotes, whereas type 2 isoform (IDI‐2) flavoenzyme bacteria completely absent human. IDI‐2 pathogenic bacterium Streptococcus pneumoniae was recombinantly expressed Escherichia coli . Steady‐state kinetic studies of indicated FMNH ( K M =0.3 μ ) bound before isopentenyl...
Worldwide, invasive candidiasis are a burden for the health system due to difficulties manage patients, increasing of resistance current therapeutics and emergence naturally resistant species Candida. In this context, development innovative antifungal drugs is urgently needed. During candidiasis, yeast submitted many stresses (oxidative, thermic, osmotic) in human host. order resist develops different strategy, especially biosynthesis trehalose. Starting from 3D structural data TPS2, an...
Isopentenyl-diphosphate (IPP):dimethylallyl diphosphate isomerase is a key enzyme in the biosynthesis of isoprenoids. The mechanism isomerization reaction involves protonation unactivated carbon-carbon double bond substrate, but identity acidic moiety providing proton still not clear. Multiple sequence alignments and geometrical features observed crystal structures complexes with IPP suggest that Tyr-104 could play an important role during catalysis. A series mutants was constructed by...