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 »
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 »
X-Ray Experiments Zero in on COVID-19 Antibodies
In the fight against SARS-CoV-2, scientists have been working on identifying neutralizing antibodies that could be used in preventative treatments or as post-exposure therapies. The latest findings, which include data from the ALS, indicate that antibodies from SARS survivors could potently block entry of SARS-CoV-2 into host cells. Read more »
Study Leads to Firmer Grasp of Biochemical “Reactive Handle”
Protein crystallography provided new insight into a functional group of molecules that, if added to bacterial enzymes, could enable a variety of alterations to the bacteria’s polymer output. Tweaking enzymes to produce these “reactive handles” is a first step toward biosynthesizing diverse polymers with tailored properties. Read more »
Staff at Berkeley Lab’s X-Ray Facility Mobilize to Support COVID-19-Related Research
X-rays allow researchers to map out the 3D structure of proteins relevant to diseases at the scale of molecules and atoms, and the ALS has been recalled to action to support research related to COVID-19, the coronavirus disease that has already infected about 2 million people around the world. Read more »
ALS Reveals Vulnerability in Cancer-Causing Protein
A promising anticancer drug, AMG 510, was developed by Amgen Inc. with the help of novel structural insights gained from protein structures solved at the ALS. AMG 510, which is currently in phase II clinical trials for efficacy, targets tumors caused by mutations in the KRAS protein, one of the most common causes of cancer. Read more » 
77Se NMR Probes the Protein Environment of Selenomethionine
Sulfur is critical for protein structure and function but lacks a sensitive isotope for nuclear magnetic resonance (NMR) experiments. This can be circumvented by substituting sulfur with selenium, which has an NMR-compatible isotope (77Se). To enable interpretation of the NMR data, the structures of five of protein variants were solved by x-ray crystallography to a resolution of 1.2 Å. Read more »
Discovery of a Covalent Inhibitor of KRASG12C (AMG 510) for the Treatment of Solid Tumors
KRASG12C has emerged as a promising target in the treatment of solid tumors; however, clinically viable inhibitors have yet to be identified. Here, researchers report on structure-based design and optimization efforts, culminating in the identification of AMG 510, a highly potent, selective, and well-tolerated KRASG12C inhibitor currently in phase I clinical trials (NCT03600883). Read more »
Genetic Blueprint for the Bioproduction of an Antidepressant Drug Candidate
A set of genes from a marine bacterium has been found to encode the biosynthesis of a promising antidepressant drug candidate. This work, which used the ALS to solve the structure of a key enzyme, could enable industrial-scale bioproduction of the drug in ways that are more efficient and sustainable than chemical synthesis. Read more »
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