A number of clinically validated drugs have been developed by repurposing the CUL4-DDB1-CRBN-RBX1 (CRL4CRBN) E3 ubiquitin ligase complex with molecular glue degraders to eliminate disease-driving proteins. Here, we present the identification of a first-in-class GSPT1-selective cereblon E3 ligase modulator, CC-90009, that targets acute myeloid leukemia blasts and leukemia stem cells. Read more »
ALS Work Using Protein Crystallography
Protein crystallography is used for determining the molecular structure of proteins. Crystallized protein molecules cause a beam of incident x-rays to scatter in many directions, with constructive and destructive interference generating a diffraction pattern. By analyzing these patterns, a crystallographer can produce a three-dimensional picture of the density of electrons within the crystal and thus determine the protein's structure.
Inhalable COVID-19 Protection via Synthetic Nanobodies
Protein structures obtained in part at the ALS helped researchers to increase the potency of simplified antibodies (nanobodies) designed to neutralize SARS-CoV-2. Stable enough to be used in inhalers or nasal sprays, the nanobodies offer a new option, aside from injected vaccines, for COVID-19 prevention and treatment. Read more »
The Odd Structure of ORF8: Scientists Map the Coronavirus Protein Linked to Immune Evasion and Disease Severity
Researchers determined the atomic structure of a coronavirus protein thought to help the pathogen evade and dampen response from human immune cells. Researchers determined the atomic structure of a coronavirus protein thought to help the pathogen evade and dampen response from human immune cells. Read more »
Newly Discovered Photosynthesis Enzyme Yields Evolutionary Clues
Scientists have discovered a primitive form of rubisco, a photosynthesis enzyme that has helped shape life on Earth. Detailed information about its structure, determined using complementary techniques at the ALS, will help scientists understand how carbon-fixing organisms oxygenated the atmosphere and how modern plants evolved. Read more »
Domain-Swap Dimerization of Acanthamoeba castellanii CYP51 and a Unique Mechanism of Inactivation by Isavuconazole
We investigated the mechanism of action of antifungal drugs in the human pathogen Acanthamoeba castellanii. We discovered that the enzyme target formed a dimer via an N-termini swap, whereas drug-bound AcCYP51 was monomeric. Cover image shows a molecular model of the AcCYP51 dimer in a phospholipid bilayer. Read more »
Experimental Drug Targets HIV in a Novel Way
Researchers from Gilead Sciences Inc. solved the structure of an experimental HIV drug bound to a novel target: the capsid protein that forms a shield around the viral RNA. The work could lead to a long-lasting HIV treatment that overcomes the problem of drug resistance and avoids the need for burdensome daily pill-taking. Read more »
Jennifer Doudna and the Nobel Prize: The Advanced Light Source Perspective
The 2020 Nobel Prize in Chemistry was awarded to Jennifer Doudna and Emmanuelle Charpentier for the development of a world-changing gene-editing technology. At the ALS, Doudna’s work on CRISPR-Cas9 was enabled by many visionary people with innovative ideas, implemented in support of a world-class structural biology program. Read more »
Study Finds ‘Missing Link’ in the Evolutionary History of Carbon-Fixing Protein Rubisco
Scientists discovered an ancient form of rubisco, the most abundant enzyme on Earth and critical to life as we know it. Found in previously unknown environmental microbes, the newly identified rubisco provides insight into the evolution of the photosynthetic organisms that underlie the planet’s food chains. Read more »
Targeting the trypanosome kinetochore with CLK1 protein kinase inhibitors
Saldivia et al. identify CLK1 as the target for the amidobenzimidazoles series of compounds. Inhibition of this protein kinase impairs inner kinetochore recruitment, causing cell-cycle arrest and cell death in trypanosomal pathogens such as Trypanosoma brucei. Read more »
Providing New Technologies for Vaccine Development
Antigens can sometimes be attached to a protein scaffold to mimic the shape of a virus and elicit a stronger immune response. Scientists developed a method to design such proteins, and ALS data helped to visualize the atomic structure and determine the dynamics of the designed scaffolds. Read more »
- « Previous Page
- 1
- 2
- 3
- 4
- 5
- 6
- …
- 14
- Next Page »