Researchers identified a compound that disrupts a hard-to-target tumor growth pathway in breast, lung, and other cancers and used the ALS to characterize the chemical interactions critical to its potency. This work contributed to the development of a similar compound currently undergoing clinical trials in cancer patients, and informs hypotheses for designing better drug candidates. 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.
AI Delivers Rapid, Precise Design of Tumor-Targeting Protein
A new protein designed using AI can precisely recognize a key therapeutic target for cancer. X-ray crystallography data collected at the ALS confirmed the new protein’s specificity for its target, demonstrating a configurable and scalable approach to cancer therapy. Read more »![]()
X-Rays Shed Light on Possible New Treatments for TB
Using ALS beamlines, a new study revealed how CMX410 inhibits Pks13, a cell wall enzyme in Mycobacterium tuberculosis, the bacterium responsible for tuberculosis. CMX410 is effective against drug-sensitive and drug-resistant strains of the bacterium and has been proven safe in multiple animal models of infection. Read more »
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Sharks Shed Light on Origins of Adaptive Immune System
A team of researchers identified the three-dimensional structure of a protein expressed by a gene of a modern nurse shark that is proposed to be a close homologue to a gene that, more than 500 million years ago, gave rise to the adaptive immune system shared by all vertebrates. By understanding the emergence and evolution of the immune system, researchers may advance work in immunology, genetics, and biotechnology.
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Researchers Identify Viral Swiss Army Knife, Clarifying How Replication Occurs
Viruses are ingenious, infectious agents, capable of replicating inside the living cells of a host organism. Enterovirus, a common viral pathogen, is responsible for a range of diseases from mild colds to severe conditions, including viral meningitis, myocarditis, and paralysis. A new study sheds light on how enteroviruses use structured RNA elements and multifunctional proteins to coordinate viral replication efficiently using minimal genetic material. Read more »
ALS Captures Structure of Engineered Protein, Opening New Options to Treat IBD
Researchers use the ALS to confirm the structure of an engineered immune protein that could open new opportunities to treat inflammatory bowel disease. Read more »
Deep-Dive Inspection of a Molecular Assembly Line
By locking down certain movable parts of a modular drug-building protein, researchers learned new details about how carrier proteins transfer the product protein between modules. The results offer insights that could enable scientists to design and create new and improved medicines, such as antibiotics, using synthetic biology. Read more »
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Identification of Structurally Novel KRASG12C Inhibitors through Covalent DNA-Encoded Library Screening
DNA-encoded library (DEL) technology was used to prepare a ~1.6 × 107-compound cysteine-reactive library (representative component shown at bottom, cysteine-reactive site indicated). Screening this library against the KRASG12C oncoprotein identified multiple structurally novel inhibitors of this challenging-to-drug target (e.g., frontmost green compound in the X-ray structure at right, covalent bond to KRASG12C indicated). Read more »
Identification and Structural Characterization of Antibodies for Severe Malaria
Researchers used x-ray crystallography at the ALS to characterize how two newly discovered antibodies prevent the protein interactions responsible for severe malaria. Understanding this mechanism offers novel insights for vaccine development. Read more »
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Structure of the human autophagy factor EPG5 and the molecular basis of its conserved mode of interaction with Atg8-family proteins
The study reports the first structure of human EPG5 (HsEPG5) determined by cryo-EM and AlphaFold2 modeling. Read more »
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