To engineer crops with higher levels of the important amino acid, lysine, researchers solved the structure of an enzyme that helps break down lysine in plants. A fuller understanding of the factors affecting lysine levels should aid in the successful development of stable high-lysine crops to combat malnutrition globally. 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.
How Proteins Remodel DNA in Bacteria under Stress
Multiscale, multimodal visualization techniques at the ALS enabled researchers to clarify how proteins remodel bacterial DNA in response to stressful environments. The discovery could lead to new strategies for controlling microbial behavior and, eventually, new ways to fight bacterial infections. Read more »
Structural Features Mediating Zinc Binding and Transfer in the AztABCD Zinc Transporter System
Zinc homeostasis is critical for bacterial survival and virulence. Extracellular zinc-binding proteins play an important role in this process. This work assesses the role of several flexible or unstructured sequences in zinc binding and transfer from proteins AztD to AztC. The results provide insights into the dynamic nature of these processes and support a previously proposed structural model of transfer. Read more »
Rotavirus VP3 Is a Multifunctional Capping Machine
Rotavirus, a major cause of infantile gastroenteritis, is responsible for the deaths of about 200,000 children per year. Although vaccines are available, the virus still circulates, and a fuller understanding of the viral structures is needed. Here, scientists investigate the structure and function of the last unsolved rotavirus structural protein. Read more »
Evaluation of Free Energy Calculations for the Prioritization of Macrocycle Synthesis
Free energy perturbation methods represent a paradigm shift in drug discovery, where computational methods inform benchtop activities. Macrocycles are highly constrained molecules, often resulting in nonintuitive structure–activity relationships requiring lengthy synthetic routes. Free energy perturbation methods can be used to predict potency, guiding synthetic chemistry efforts to de-risk complex synthesis. Read more »
Antibody from SARS Survivor Neutralizes SARS-CoV-2
Using structural data from the ALS and cryo-electron microscopy, researchers have characterized how an antibody binds to and neutralizes SARS-CoV-2. This work provides the basis for therapeutic and vaccine development for the SARS-CoV-2 virus, which is responsible for the COVID-19 pandemic. Read more »
Crystal structure of the catalytic subunit of bovine pyruvate dehydrogenase phosphatase
The crystal structure of the catalytic subunit of bovine pyruvate dehydrogenase phosphatase provides new insights into the mechanism of the regulation of the activity of the pyruvate dehydrogenase complex. Read more »
Study Gains New Insight Into Bacterial DNA Packing
When bacteria are put in different environments, their genes start to adapt remarkably quickly because the proteins making up their chromosomes can pack and unpack rapidly. Researchers have now imaged this process at the molecular level, a discovery that could eventually enable scientists to develop strategies to control microbial behavior. Read more »
On-Off Switch for Regulating Tumor-Cell Growth
The mechanisms that affect the regulation of cell growth in certain tumor cells were revealed by a Genentech study of enzyme structures, conducted in part at the ALS. The work establishes a framework for the rational discovery of new therapeutics to improve upon currently existing treatments for certain cancers. Read more »
How a Cancer Drug Targets Proteins for Degradation
Protein structures obtained by Novartis researchers helped reveal how a cancer drug promotes the degradation of proteins essential to cell proliferation. A detailed understanding of the drug’s mechanism of action is key to determining whether the protein-degradation system can be reprogrammed to degrade different targets. Read more »
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