LONP1 is an AAA+ protease that maintains mitochondrial homeostasis by removing damaged or misfolded proteins. Elevated activity and expression promotes cancer cell proliferation and resistance to apoptosis-inducing reagents. Herein, we report the development of selective boronic acid-based LONP1 inhibitors using structure-based drug design as well as the first structures of human LONP1 bound to various inhibitors. 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.
To Design Truly Compostable Plastic, Scientists Take Cues From Nature
Researchers have designed an enzyme-activated compostable plastic that could diminish microplastics pollution and holds great promise for plastics upcycling. The material can be broken down to its building blocks—small individual molecules called monomers—and then reformed into a new compostable plastic product. Read more »
X-Ray Study Recasts Role of Battery Material from Cathode to Catalyst
Researchers used the ALS to learn about a lithium-rich battery material that has been the subject of much study for its potential to extend the range of electric vehicles and the operation of electronic devices. Through a fundamental spectroscopic study, they not only clarified the reaction mechanism of this material, but also found a conceptually different use of it as a catalyst. Read more »
Targeting KRAS Mutant Cancers via Combination Treatment: Discovery of a 5-Fluoro-4-(3H)-quinazolinone Aryl Urea pan-RAF Kinase Inhibitor
The cover feature shows a chessboard (representative of KRAS mutant cells) and how the concerted action of the MEK inhibitor cobimetinib (rook) and the new selective pan-RAF inhibitor GNE-0749 (queen) force the opposing king (phospho-ERK, the downstream signaling node of RAF and MEK) into checkmate. Read more »
Designing Selective Membranes for Batteries Using a Drug Discovery Toolbox
Researchers designed a polymer membrane with molecular cages built into its pores that hold positively charged ions from a lithium salt. These “solvation cages” increased lithium-ion flow by an order of magnitude and could allow high-voltage battery cells to operate at higher power and more efficiently, important for both electric vehicles and aircraft. Read more »
Study Shines New Light on Li-Battery Cathode Materials
Researchers clarified key reaction mechanisms in a Li-battery cathode material, revealing its surprising utility as a catalyst for next-gen batteries. The work refutes widely held ideas about reversible reactions in a highly debated material for Li-based batteries and expands the range of materials suitable for use in high-power batteries and fuel cells. Read more »
Mystery Protein Helps COVID–19 Avoid Immunity
Using the Advanced Light Source (ALS), researchers solved the structure of ORF8, a protein specific to SARS-CoV-2. Understanding the structure of ORF8 opens the door to therapy studies targeting SARS-CoV-2, the virus responsible for causing COVID-19. Read more »
Chiral Spin Textures in Amorphous Iron–Germanium Thick Films
Robert Streubel and co‐workers report the formation of topological magnetization vector fields in disordered materials with local inversion symmetry breaking, harnessing high‐resolution Lorentz microscopy, quantitative x‐ray microspectroscopy, and coherent scattering. The image shows the reconstructed in‐plane magnetic induction of closely packed Bloch skyrmions embedded into helical spins. Read more »
Probing Composite Materials to Make Better Batteries
Researchers found that when an ion-conducting polymer composite is placed in an electric field, it forms ion-rich hotspots that continue to grow for hours after the field is removed. The study opens a new path to understanding the dynamic structure of composite materials for smaller, lighter batteries. Read more »
Construction, characterization and crystal structure of a fluorescent single-chain Fv chimera
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 »
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