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 »
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.
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 »
ALS Passes the 7000-Protein Milestone
The eight structural biology beamlines at the ALS have now collectively deposited over 7000 proteins into the Protein Data Bank (PDB), a worldwide, open-access repository of protein structures. The 7000th ALS protein (entry no. 6C7C) is an enzyme from Mycobacterium ulcerans (strain Agy99), solved with data from Beamline 5.0.2. Read more »
Respiratory Virus Study Points to Likely Vaccine Target
Respiratory syncytial virus (RSV) causes serious respiratory disease in infants and older adults, but no vaccine is yet available. Researchers have now determined the molecular structures of human antibodies bound to an RSV surface protein, providing a promising route for designing a vaccine effective against a broad range of RSV strains. Read more »
Structure-based Design of Pyridone–Aminal eFT508 Targeting Dysregulated Translation by Selective Mitogen-activated Protein Kinase Interacting Kinases 1 and 2 (MNK1/2) Inhibition
Dysregulated translation drives key hallmarks of cancer and is controlled by Phase 2 candidate eFT508 binding to the MNK protein, exploiting stereoelectronic interactions, critical to the compound’s selectivity and potency. Read more »
Modified Antibody Clarifies Tumor-Killing Mechanisms
An antibody was modified to activate a specific pathway of the immune system, demonstrating its value in killing tumor cells. The work provides a platform for disentangling different immune-system pathways and could lead to the design of improved immunotherapies. Read more »
Genentech Advances Research Toward Better Medicines to Lower Cholesterol
Genentech has been working in collaboration with the ALS for years with the goal of identifying a better cholesterol treatment mechanism that targets a cholesterol-regulating protein in the body known as PCSK9. Recent advances in understanding PCSK9’s structure have put them closer to that goal. Read more »
NIH Grant Will Enhance Structural Biology Research Experience for ALS Users
A recently awarded National Institutes of Health (NIH) grant will help integrate existing structural biology resources at the ALS to better serve users. The funds will help establish a centralized collaborative mechanism, called ALS-ENABLE, that will guide users through the most appropriate routes for answering their biological questions. Read more »
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