Researchers used several analytical techniques at the ALS to demonstrate how soft-tissue structures may be preserved in dinosaur bones, countering long-standing scientific dogma that protein-based body parts cannot survive more than one million years. Read more »
X-ray Crystal Structures of the Influenza M2 Proton Channel Drug-Resistant V27A Mutant Bound to a Spiro-Adamantyl Amine Inhibitor Reveal the Mechanism of Adamantane Resistance
The M2 proton channel, shown with front and back monomer helices removed, is an anti-influenza drug target. Here, a bound inhibitor blocks the transport of protons through the V27A mutant channel. 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 »
Berkeley Lab Helps Reveal How Dinosaur Blood Vessels Can Preserve Through the Ages
A team of scientists used infrared and x-ray imaging performed at the Advanced Light Source to determine the chemical mechanisms that allow soft tissue structures to persist in dinosaur bones—countering the long-standing scientific dogma that protein-based body parts can’t survive more than 1 million years. Read more »
X-Ray Technology Sheds New Light on Antibiotic Synthesis
Atomic-scale structural analyses performed at the ALS are helping scientists understand the inner workings of the enzyme “assembly lines” that microbes use to produce an important class of compounds, many of which have uses as antibiotics, antifungals, and immunosuppressants. Read more »
Turning Up the Heat on Antibacterial-Resistant Diseases
Scientists have designed a biocompatible polymer that has the potential to advance photothermal therapy, a technique that deploys near-infrared light to combat antibacterial-resistant infections and cancer. The team synthesized the polymer by stringing together small molecules called ionic azaquinodimethanes, which they characterized at the ALS. Read more »
Molecular Handle Enables Viral Attack on Joint Cells
A collaboration of university and industry researchers used x-ray crystallography to investigate how the chikungunya virus, which can cause debilitating joint pain, engages a receptor protein found on the surfaces of joint cells. The work provides a path forward in the fight against a family of viruses that can result in acute and chronic arthritis. Read more »
Unique Cancer Drug Discovered With Help From Advanced Light Source Begins Historic Clinical Trial
Errors in the KRAS gene, which encodes a crucial cell-signaling protein, are one of the most common causes of cancer. Seeking to develop a long-sought direct inhibitor, researchers at Amgen conducted x-ray crystallography of KRAS(G12C) proteins at the ALS. The high-resolution structural maps helped Amgen make the breakthrough discovery of a small pocket on the molecule. Read more »
Structural Basis for Finding OG Lesions and Avoiding Undamaged G by the DNA Glycosylase MutY
Finding OG and avoiding G: DNA repair enzyme MutY distinguishes between undamaged guanine (green) and oxidized guanine when targeting OG:A mispairs. A structural motif within the C-terminal domain (violet) responds to OG to G substitution and appears mechanistically coupled to the adenine removal site (gray) in the N-terminal domain (cyan). 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 »
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