A5050257457- Peroxisome Proliferator-Activated Receptors
- Microtubule and mitosis dynamics
- Lipid metabolism and biosynthesis
- Cancer Treatment and Pharmacology
- Cancer, Hypoxia, and Metabolism
- Chemical Synthesis and Characterization
- Pain Management and Opioid Use
- Genomics and Chromatin Dynamics
- Pharmacological Effects and Toxicity Studies
- Cellular transport and secretion
- Metabolism, Diabetes, and Cancer
- Epigenetics and DNA Methylation
- Metabolism and Genetic Disorders
- Pain Mechanisms and Treatments
- Polyoxometalates: Synthesis and Applications
- Chemical Synthesis and Reactions
- Fungal and yeast genetics research
- Molecular Sensors and Ion Detection
- Nanoparticle-Based Drug Delivery
- Electrospun Nanofibers in Biomedical Applications
- Neurogenetic and Muscular Disorders Research
- Silicone and Siloxane Chemistry
- Neurological Complications and Syndromes
- RNA Research and Splicing
- Migraine and Headache Studies
Max Planck Institute of Molecular Physiology
2018-2024
University Hospital Cologne
2022
University of Cologne
2022
University of Pavia
2012-2018
Centre Hospitalier Universitaire de Nice
2011-2012
Hôpital Pasteur
2011
Open (O) and closed (C) topologies of HORMA-domain proteins are respectively associated with inactive active states fundamental cellular pathways. The HORMA protein O-MAD2 converts to C-MAD2 upon binding CDC20. This is rate limiting for assembly the mitotic checkpoint complex (MCC), effector a required fidelity. A catalyst assembled at kinetochores accelerates MAD2:CDC20 association through poorly understood mechanism. Using reconstituted SAC system, we discovered that CDC20 an impervious...
Delivery of native or chemically modified recombinant proteins into mammalian cells shows promise for functional investigations and various technological applications, but concerns that sub-cellular localization integrity delivered may be affected remain high. Here, we surveyed batch electroporation as a delivery tool single polypeptides multi-subunit protein assemblies the kinetochore, spatially confined well-studied subcellular structure. After human cells, fluorescent Ndc80 Mis12...
Dysregulated ether lipid metabolism is an important hallmark of cancer cells. Previous studies have reported that lowering levels by genetic ablation the lipid-generating enzyme alkyl-glycerone phosphate synthase (AGPS) lowers key structural and oncogenic alters fatty acid, glycerophospholipid, eicosanoid to impair pathogenicity, indicating AGPS may be a potential therapeutic target for cancer. In this study, we performed small-molecule screen identify candidate inhibitors. We identified...
The spindle assembly checkpoint (SAC) safeguards the genome during cell division by generating an effector molecule known as Mitotic Checkpoint Complex (MCC). MCC comprises two subcomplexes: BUBR1:BUB3 and CDC20:MAD2, formation of CDC20:MAD2 is rate-limiting step assembly. Recent studies show that rate significantly accelerated cooperative binding CDC20 to SAC proteins MAD1 BUB1. However, molecular basis for this acceleration not fully understood. Here, we demonstrate structural flexibility...
Use of high doses verapamil in preventive treatment cluster headache (CH) is limited by cardiac toxicity. We systematically assess the safety very dose (verapamil VHD) CH patients. Our work was a study performed two French centers (Marseilles–Nice) from 12/2005 to 12/2008. patients treated with VHD (≥720 mg) were considered systematic electrocardiogram (EKG) monitoring. Among 200 patients, 29 (14.8%) used (877 ± 227 mg/day). Incidence EKG changes 38% (11/29). Seven (24%) presented...
Despite its great potential, the target-based approach has been mostly unsuccessful in tuberculosis drug discovery, while whole cell phenotypic screening delivered several active compounds. However, for many of these hits, cellular target not yet identified, thus preventing further optimization In this context, newly validated CTP synthetase PyrG was exploited to assess a already known, but untargeted, antimycobacterial To purpose publically available GlaxoSmithKline compound set assayed,...
The precursor of the essential ether phospholipids is synthesized by a peroxisomal enzyme that uses flavin cofactor to catalyze reaction does not alter redox state substrates. crystal structure reveals V-shaped active site with narrow constriction in front prosthetic group. Mutations causing inborn phospholipid deficiency, very severe genetic disease, target residues are part catalytic center. Biochemical analysis using substrate and analogs, absorbance spectroscopy, mutagenesis, mass...
The spindle assembly checkpoint (SAC) makes mitotic exit contingent on completion of sister chromatid biorientation, but how this coordination is achieved in practice remains poorly understood. Kinetochores, megadalton chromosome attachment sites to microtubules, contribute SAC signaling. However, it unclear whether kinetochores are mere docking for proteins, or further co-orientation catalysts, including MAD1:MAD2 and BUB1:BUB3, facilitate Here, we combined biochemical reconstitutions the...
Although the precise functions of ether phospholipids are still poorly understood, significant alterations in their physiological levels associated either to inherited disorders or aggressive metastatic cancer. The essential precursor, alkyl-dihydroxyacetone phosphate (DHAP), for all species is synthetized two consecutive reactions performed by enzymes sitting on inner side peroxisomal membrane. Here, we report characterization recombinant human DHAP acyl-transferase, which performs first...
Abstract The spindle assembly checkpoint (SAC) safeguards the genome during cell division by generating an effector molecule known as Mitotic Checkpoint Complex (MCC). MCC comprises two subcomplexes, and its assembly, formation of CDC20:MAD2 subcomplex is rate-limiting step. Recent studies show that rate significantly accelerated cooperative binding CDC20 to SAC proteins MAD1 BUB1. However, molecular basis for this acceleration not fully understood. Here, we demonstrate structural...