A5001850767- Microtubule and mitosis dynamics
- Cell Adhesion Molecules Research
- Chronic Lymphocytic Leukemia Research
- RNA modifications and cancer
- Peptidase Inhibition and Analysis
- Nerve injury and regeneration
- Biochemical and Molecular Research
- Cancer Mechanisms and Therapy
- RNA and protein synthesis mechanisms
- Melanoma and MAPK Pathways
- Glycosylation and Glycoproteins Research
- Monoclonal and Polyclonal Antibodies Research
- NF-κB Signaling Pathways
- Neuroscience and Neuropharmacology Research
- Protease and Inhibitor Mechanisms
- Cancer-related Molecular Pathways
- Protein Degradation and Inhibitors
- Protein Kinase Regulation and GTPase Signaling
- Ubiquitin and proteasome pathways
- HER2/EGFR in Cancer Research
- Click Chemistry and Applications
- Photosynthetic Processes and Mechanisms
- Lymphoma Diagnosis and Treatment
- Signaling Pathways in Disease
- Protein Tyrosine Phosphatases
Biogen (United States)
2014-2024
Howard Hughes Medical Institute
1999-2020
University of Lausanne
2006
Biogen (Switzerland)
2005
University of California, Davis
2003
Harvard University
2001
Boston University
2001
Yale University
1998
Whitney Museum of American Art
1998
Isoleucyl-transfer RNA (tRNA) synthetase (IleRS) joins Ile to tRNA(Ile) at its synthetic active site and hydrolyzes incorrectly acylated amino acids editing site. The 2.2 angstrom resolution crystal structure of Staphylococcus aureus IleRS complexed with Mupirocin shows the acceptor strand in continuously stacked, A-form conformation 3' terminal nucleotide To position terminus site, must adopt hairpinned seen tRNA(Gln) synthetase. acid activity may result from incorrect products shuttling...
Abstract Bruton's tyrosine kinase (BTK), a member of the TEC family kinases, plays crucial role in B‐cell maturation and mast cell activation. Although structures unphosphorylated mouse BTK domain phosphorylated domains human ITK are known, understanding selectivity profiles inhibitors has been hampered by lack availability high resolution, ligand‐bound structure. Here, we report crystal bound to either Dasatinib (BMS‐354825) at 1.9 Å resolution or...
Abstract Monoclonal antibodies (Mabs) are a favorite drug platform of the biopharmaceutical industry. Currently, over 20 Mabs have been approved and several hundred others in clinical trials. The anti‐LINGO‐1 Mab Li33 was selected from large panel by Fab phage display technology based on its extraordinary biological activity promoting oligodendrocyte differentiation myelination vitro animal models remyelination. However, had poor solubility when converted into full antibody an immunoglobulin...
Background: Aminoacyl-tRNA synthetases covalently link a specific amino acid to the correct tRNA. The fidelity of this reaction is essential for accurate protein synthesis. Each synthetase has molecular mechanism distinguish pair substrates from pool acids and isologous tRNA molecules. In case glutaminyl-tRNA (GlnRS) prior binding required activation glutamine by ATP. A complete understanding specificity in GlnRS requires determination structure with both bound.Results: stable...
BIO8898 is one of several synthetic organic molecules that have recently been reported to inhibit receptor binding and function the constitutively trimeric tumor necrosis factor (TNF) family cytokine CD40 ligand (CD40L, aka CD154). Small molecule inhibitors protein-protein interfaces are relatively rare, their discovery often very challenging. Therefore, understand how achieves this feat, we characterized its mechanism action using biochemical assays X-ray crystallography. inhibited soluble...
The oligomeric state of BAFF (B cell activing factor), a tumor necrosis factor (TNF) family cytokine that plays critical role in B development and survival, has been the subject recent debate. Myc-tagged starting at residue Gln136 was previously reported to crystallize as trimers pH 4.5, whereas histidine-tagged construct BAFF, Ala134, formed virus-like cluster containing 60 monomers when crystallized 9.0. formation 60-mer dependent, requiring >or= 7.0. More recently, suggested be...
The nuclear hormone receptor RORγ regulates transcriptional genes involved in the production of pro-inflammatory interleukin IL-17 which has been linked to autoimmune diseases such as rheumatoid arthritis, multiple sclerosis and inflammatory bowel disease. This activity is modulated through a protein-protein interaction involving activation function 2 (AF2) helix on ligand binding domain conserved LXXLL motif coactivator proteins. Our goal was develop specific inverse agonist that would help...
MLKL is a pore forming pseudokinase involved in the final stage of necroptosis, form programmed cell death. Its phosphorylation by RIPK3 necessary for triggering necroptosis but not apoptosis, which makes it unique target pharmacological inhibition to block necroptotic This mechanism has been described as playing role disease progression neurodegenerative and inflammatory diseases. A type II kinase inhibitor (cpd 1) that reportedly binds domain prevents necroptosis. Here we describe five...
The Nogo66 receptor (NgR1) is a neuronal, leucinerich repeat (LRR) protein that binds three central nervous system (CNS) myelin proteins, Nogo, myelin-associated glycoprotein, and oligodendrocyte mediates their inhibitory effects on neurite growth. Although the LRR domains NgR1 are necessary for binding to exact epitope(s) involved in ligand unclear. Here we report generation detailed characterization of an anti-NgR1 monoclonal antibody, 7E11. 7E11 antibody blocks glycoprotein with...
Artemin (ART) promotes the growth of developing peripheral neurons by signaling through a multicomponent receptor complex comprised transmembrane tyrosine kinase (cRET) and specific glycosylphosphatidylinositol-linked co-receptor (GFRalpha3). Glial cell line-derived neurotrophic factor (GDNF) signals similar ternary but requires heparan sulfate proteoglycans (HSPGs) for full activity. HSPG has not been demonstrated as requirement ART signaling. We crystallized in presence solved its...
Pharmacological activation of the E3 ligase Parkin represents a rational therapeutic intervention for treatment Parkinson's disease. Here we identify several compounds that enhance activity wildtype in presence phospho-ubiquitin and act as positive allosteric modulators (PAMs). While these activate series biochemical assays, they do not by thermally destabilizing fail to translocation rate mitochondria or enact mitophagy cell-based assays. We conclude context cellular milieu window...
Protein interacting with C kinase (PICK1) is a scaffolding protein that present in dendritic spines and interacts wide array of proteins through its PDZ domain. The best understood function PICK1 regulation trafficking AMPA receptors at neuronal synapses via specific interaction the GluA2 subunit. Disrupting PICK1-GluA2 has been shown to alter synaptic plasticity, molecular mechanism learning memory. Lack potent, selective inhibitors domain hindered efforts exploring as therapeutic target...