In vitro display technologies based on phage and yeast have a successful history of selecting single-chain variable fragment (scFv) antibodies against various targets. However, single-chain antibodies are often unstable and poorly expressed. We explore the feasibility of converting scFv antibodies to an intrinsically fluorescent format by inserting a monomeric, stable fluorescent protein between the light- and heavy-chain variable regions. Read more »
ALS Work Using Scattering/Diffraction
These techniques make use of the patterns of light produced when x-rays are deflected by the closely spaced lattice of atoms in solids and are commonly used to determine the structures of crystals and large molecules such as proteins.
CC-90009, a novel cereblon E3 ligase modulator, targets acute myeloid leukemia blasts and leukemia stem cells
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 »
Stacking the Deck for Custom-Built Hybrid Materials
Researchers fabricated an electronically coupled heterostructure from a novel semiconducting 2D polymer and a 2D transition metal dichalcogenide. Dramatic optical and electronic changes emerged as polymer thickness decreased, underscoring the potential for the discovery of emergent phenomena in studies of hybrid heterostructures. Read more »
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 »
Molecular Complex Removes Copper Ions from Water
X-ray analyses provided key insights into the copper uptake mechanisms in a new organic-inorganic hybrid material that quickly and selectively removes copper ions from water. The material provides an efficient tool for copper remediation as well as a blueprint for creating other hybrid materials for removing toxic metals from water. 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 »
Functionalization of Benzotriazole-Based Conjugated Polymers for Solar Cells: Heteroatom vs Substituents
Understanding the structure-property relationship is important when designing new conjugated polymers for high-efficiency polymer solar cells. Rech et al. systematically explore the impact of a variety of functional groups, including nitrogen heteroatoms, fluorine substituents, and cyano groups. 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 »
Scientists Design New Framework for Clean Water
A promising solution to water pollution from abandoned copper mines relies on materials that adsorb copper ions from wastewater, but commercially available products lack the required chemical specificity and load capacity. A team of scientists has designed a new crystalline material that targets and traps copper ions from wastewater with unprecedented precision and speed. Read more »
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