While the SHP2 protein helps regulate cellular activity, mutations in its structure can lead to cancer. X-ray crystallography at the ALS and SSRL has revealed differences between normal and mutated SHP2, as well as how it binds to certain cancer drugs. These structural insights open the door to new types of cancer therapy. 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.
A Two-Pronged Defense against Bacterial Self-Intoxication
Researchers solved the structure of a bacterial toxin bound to a neutralizing protein, revealing two distinct mechanisms for how the toxin-producing bacteria avoid poisoning themselves. The findings offer clues to the evolutionary origins of the potent toxins that enable bacterial pathogens to cause human diseases such as cholera and diphtheria. Read more »
Toward a Blueprint for Anti-influenza Drugs
Researchers obtained high-resolution structures of several influenza antiviral drug molecules bound to their proton-channel targets in both open and closed conformations. The structures provide an atomic-level blueprint from which to design more effective anti-influenza drugs that can overcome growing drug resistance. Read more »
Inhibitors of the M2 Proton Channel Engage and Disrupt Transmembrane Networks of Hydrogen-Bonded Waters
The influenza M2 proton channel can bind to drugs and inhibitors. The ammonium groups of these compounds form hydrogen bonds with networks of ordered waters within the channel, and the adamantyl groups sterically block the diffusion of hydronium into the channel pore. Read more »
Antibody Therapy for Autoimmune Diseases
The balance between two types of white blood cells is disrupted in autoimmune diseases. Using protein crystallography, scientists have identified a human antibody that locks interleukin-2, a signaling protein, in a conformation that preferentially activates one cell type to restore the balance and treat autoimmune diseases. Read more »
Targeting Bacteria That Cause Meningitis and Sepsis
Researchers determined the structure of a human antibody that broadly protects against a bacterium that causes meningitis and sepsis. The work provides molecular-level information about how the antibody confers broad immunity against a variable target and suggests strategies for further improvement of available vaccines. Read more »
Unwinding a Quadruple Helix
The double helix is not the only structure formed by DNA and RNA. Guanine-rich DNA and RNA sequences can fold into quadruple-helix structures called G-quadruplexes. Recently, researchers visualized the unfolding of a G-quadruplex by a protein called DHX36, gaining valuable insight into a potential target for drug development. Read more »
Structure Reveals Mechanism Behind Periodic Paralysis
X-ray crystallography of a membrane protein provided a structural understanding of how a single mutation can result in periodic muscle paralysis. The results suggest possible drug designs that could provide relief to patients with a genetic disorder that causes them to be overcome suddenly with profound muscle weakness. Read more »
Open and Shut: Pain Signals in Nerve Cells
Researchers used x-ray data to define the structure of a closed protein gate important for neuronal signaling. Comparing the closed gate with previously known structures of the same gate when open, researchers now have a comprehensive picture of proton-dependent channels in neurons. Read more »
Structures Reveal New Target for Malaria Vaccine
Researchers isolated human-derived antibodies that protect against malaria, and protein-structure studies revealed the antibodies’ site of attack. The discovery paves the way for the development of a more effective and practical human vaccine for malaria, which is responsible for half a million deaths every year. Read more »
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