- HIV Research and Treatment
- HIV/AIDS drug development and treatment
- Biochemical and Molecular Research
- Enzyme Structure and Function
- RNA modifications and cancer
- RNA and protein synthesis mechanisms
- Estrogen and related hormone effects
- Cytomegalovirus and herpesvirus research
- Retinoids in leukemia and cellular processes
- Mass Spectrometry Techniques and Applications
- RNA Research and Splicing
- Effects and risks of endocrine disrupting chemicals
- Peptidase Inhibition and Analysis
- Virus-based gene therapy research
- Viral Infectious Diseases and Gene Expression in Insects
- DNA and Nucleic Acid Chemistry
- Cancer therapeutics and mechanisms
- HIV/AIDS Research and Interventions
- Advanced biosensing and bioanalysis techniques
- Cellular transport and secretion
- Microtubule and mitosis dynamics
- Protease and Inhibitor Mechanisms
- Bioactive Compounds and Antitumor Agents
- Endoplasmic Reticulum Stress and Disease
- Autophagy in Disease and Therapy
Institut de génétique et de biologie moléculaire et cellulaire
2015-2024
Inserm
2015-2024
Université de Strasbourg
2012-2024
Centre National de la Recherche Scientifique
2015-2024
Fraunhofer Institute for Interfacial Engineering and Biotechnology
2008-2024
Biologie cellulaire et Cancer
2019-2023
Integrated Structural Biology Grenoble
2013-2020
Institut de Biologie Moléculaire et Cellulaire
1988-2017
ETH Zurich
2008
Daresbury Laboratory
2000
The crystal structure of the binary complex tRNA Asp -aspartyl synthetase from yeast was solved with use multiple isomorphous replacement to 3 angstrom resolution. dimeric synthetase, a member class II aminoacyl synthetases (aaRS's) exhibits characteristic signature motifs conserved in eight aaRS's. These three sequence are contained catalytic site domain, built around an antiparallel β sheet, and flanked by α helices that form pocket which adenosine triphosphate (ATP) CCA end bind. molecule...
LEDGF/p75 (LEDGF) is the main cellular cofactor of HIV-1 integrase (IN). It acts as a tethering factor for IN, and targets integration HIV in actively transcribed gene regions chromatin. A recently developed class IN allosteric inhibitors can inhibit LEDGF-IN interaction.
Transcription regulation by steroid hormones, vitamin derivatives, and metabolites is mediated nuclear receptors (NRs), which play an important role in ligand-dependent gene expression human health. NRs function as homodimers or heterodimers are involved a combinatorial, coordinated sequentially orchestrated exchange between coregulators (corepressors, coactivators). The architecture of DNA-bound functional dimers positions the proteins. We previously demonstrated that retinoic acid...
The crystal structure of a triple cysteine to serine mutant ERα ligand-binding domain (LBD), complexed with estradiol, shows that despite the presence tightly bound agonist ligand, protein exhibits an antagonist-like conformation, similar observed in raloxifen and 4-hydroxytamoxifen-bound structures. This mutated receptor binds estradiol wild type affinity displays transcriptional activity upon stimulation, but limited potency (about 50%). partial is efficiently repressed antagonist...
Estrogenic activity in environmental samples could be mediated through a wide variety of compounds and by various mechanisms. High-affinity for estrogen receptors (ERs), such as natural or synthetic estrogens, well low-affinity alkylphenols, phthalates, polychlorinated biphenyls are present water sediment samples. Furthermore, polycyclic aromatic hydrocarbons, which do not bind ERs, modulate means the aryl hydrocarbon receptor (AhR). In order to characterize that mediate estrogenic river...
Retroviral integration depends on the interaction between intasomes, host chromatin and cellular targeting cofactors as LEDGF/p75 or BET proteins. Previous studies indicated that retroviral integrase, by itself, may play a role in local site selection within nucleosomal target DNA. We focused our study this association analyzing intrinsic properties of various intasomes to functionally accommodate different structures lack other cofactors.Using vitro conditions allowing efficient catalysis...
Penicillin-binding proteins (PBPs) are the targets of β-lactams, most successful class antibiotics ever developed against bacterial infections. Unfortunately, worldwide and rapid spread large spectrum β-lactam resistance genes such as carbapenemases is detrimental to use in this class. New potent PBP inhibitors needed, especially compounds that resist β-lactamase hydrolysis. Here we describe structure E. coli PBP2 its Apo form upon reaction with 2 diazabicyclo derivatives, avibactam CPD4, a...
Oral presentations Session 1: Entry & uncoating O1 Host cell polo-like kinases (PLKs) promote early prototype foamy virus (PFV) replication Irena Zurnic, Sylvia Hütter, Ute Lehmann, Nicole Stanke, Juliane Reh, Tobias Kern, Fabian Lindel, Gesche Gerresheim, Martin Hamann, Erik Müllers, Paul Lesbats, Peter Cherepanov, Serrao, Alan Engelman, Dirk Lindemann O2 A novel entry/uncoating assay reveals the presence of at least two species viral capsids during synchronized HIV-1 infection Claire Da...
Insertion of retroviral genome DNA occurs in the chromatin host cell. This step is modulated by structure as nucleosomes compaction was shown to prevent HIV-1 integration and remodeling has been reported affect efficiency. LEDGF/p75-mediated targeting complex toward RNA polymerase II (polII) transcribed regions ensures optimal access dynamic that are suitable for integration. Consequently, we have investigated involvement polII-associated factors regulation integration.Using a pull down...
In the present report, a method based on chip-based nanoelectrospray mass spectrometry (nanoESI-MS) is described to detect noncovalent ligand binding human estrogen receptor alpha ligand-binding domain (hERalpha LBD). This system represents an important environmental interest, because wide variety of molecules, known as endocrine disruptors, can bind (ER) and induce adverse health effects in wildlife humans. Using proper experimental conditions, nanoESI-MS approach allowed for detection...
Integration of human immunodeficiency virus type 1 (HIV-1) into a host cell chromosome is an essential step under the control viral integrase (IN). Although this enzyme necessary and sufficient to catalyze integration reaction in vitro, cellular cofactors are involved process vivo. The chromatin-associated factor LEDGF/p75 interacts with IN promotes transcription units genome. HIV-1 also binds karyopherin TNPO3, however significance interaction during replication remains be explored.Here we...