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 »
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 Citizen-Science Computer Game for Protein Design
Using the computer game, “Foldit,” nonexpert citizen scientists designed new proteins whose structures, verified at the ALS, were equivalent in quality to and more structurally diverse than computer-generated designs. The work shows the potential of using crowd-based creativity in the design of new proteins for fighting illness and disease. Read more »
X-Ray Experiments Contribute to Studies of a Drug Now Approved to Combat Tuberculosis
The U.S. Food and Drug Administration has approved a new antibiotic that, in combination with two existing antibiotics, can tackle one of the most formidable and deadly treatment-resistant forms of the bacterium that causes tuberculosis. Studies exploring the structure and function of the new drug benefited from x-ray experiments at the ALS. Read more »
A Bullfrog’s Powerful Defense Against Toxic Red Tides
Working as a “molecular sponge,” a bullfrog protein known as saxiphilin provides powerful, yet little understood, protection against deadly neurotoxins produced in red tides. Crystallography studies at the ALS have clarified saxiphilin’s function, potentially enabling better ways to monitor and combat toxins in our oceans and food supplies. Read more »
X-Ray Studies Key in Study Relating to Immune System-Signaling Protein
A grouping of amino acids—part of an important signaling protein, STING—plays an important role in activating the immune system. A study conducted through the Collaborative Crystallography program at the ALS confirmed how this part of the STING protein helps to bind a protein-modifying enzyme associated with autoimmune diseases and some cancers. Read more »
A Frog Worth Kissing: Natural Defense Against Red Tide Toxin Found in Bullfrogs
Researchers have discovered how a protein produced by bullfrogs binds to and inhibits the action of saxitoxin, a deadly neurotoxin that causes paralytic shellfish poisoning. The findings could lead to the first-ever antidote for the compound, which blocks nerve signaling in animal muscles, causing death by asphyxiation when consumed in sufficient quantities. Read more »
Breakthrough in Membrane-Protein Design Settles Long-Standing Debate
Scientists characterized designed membrane proteins to better understand the forces that stabilize these large, complex structures. The results necessitate a rethinking of membrane-protein biophysics and could lead to better therapies for related illnesses as well as functional membrane proteins for engineering applications. Read more »
Self-Assembling 2D Arrays with de Novo Protein Building Blocks
Modular self-assembly of biomolecules in two dimensions (2D) is straightforward with DNA but has been difficult to realize with proteins, due to the lack of modular specificity similar to Watson–Crick base pairing. Here, researchers describe a general approach to designing 2D arrays using de novo designed pseudosymmetric protein building blocks. Read more »
Design and Synthesis of Selective Phosphodiesterase 4D (PDE4D) Allosteric Inhibitors for the Treatment of Fragile X Syndrome and Other Brain Disorders
PDE4D enzymes are important for normal brain function. Mutations have been asssociated with an ultrarare neurodevelopmental disorder, and genetic variation in PDE4D contributes to biological variation in human cognitive ability. Here, researchers report on novel PDE4D inhibitors providing potent memory-enhancing effects in a mouse model, with improved tolerability and reduced vascular toxicity over earlier PDE4 inhibitors. Read more »
Structural Characterization of a Synthetic Tandem-Domain Bacterial Microcompartment Shell Protein Capable of Forming Icosahedral Shell Assemblies
Bacterial microcompartments (BMCs) are subcellular compartments found in many prokaryotes, and they are of considerable interest for biotechnological applications. The BMC-H2 shell system constitutes a relatively simple generic building block that could be used to construct designed shells with a relatively highly tunable pore. Read more »
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