Using a multimodal approach that included x-ray scattering at the ALS, researchers determined how components of the SARS-CoV-2 replication mechanism fit together. A better understanding of how this protein complex works provides insight into potential structural or functional weak spots to exploit for drug development. Read more »
Deconstructing the Infectious Machinery of the SARS-CoV-2 Virus
Scientists collaborated to model the complex protein responsible for SARS-CoV-2 replication, revealing its potential weak spots for drug development. The investigation hinged on data collected from many advanced imaging techniques, including small-angle x-ray scattering (SAXS), crystallography, and small-angle neutron scattering (SANS). Read more »
Conformational Dynamics in the Interaction of SARS-CoV-2 Papain-like Protease with Human Interferon-Stimulated Gene 15 Protein
The image depicts the complex formed between SARS-CoV-2 papain-like protease and human interferon-stimulated gene 15 protein. Small-angle scattering elucidated the structural details of this complex providing insight into its role in suppressing the innate immune response and also potential routes for development of therapeutics to combat COVID-19. Read more »
Structure of blood coagulation factor VIII in complex with an anti–C1 domain pathogenic antibody inhibitor
van der Waals sphere representation of the factor VIII C1 domain, highlighting surface‐exposed hemophilia A–associated mutations that cause impaired von Willebrand factor binding and overlap with a pathogenic anti‐C1 domain inhibitor epitope. Read more »
How X-Rays Could Make Reliable, Rapid COVID-19 Tests a Reality
A highly sensitive lateral flow assay—the same type of device used in home pregnancy tests—could be developed using pairs of rigid antibodies that bind to the SARS-CoV-2 nucleocapsid protein. SAXS data showed that a particular pair of monoclonal antibodies bound to the nucleocapsid protein very strongly and stably, in part due to the antibodies’ rigidity. Read more »
Structure-Based Design of Selective LONP1 Inhibitors for Probing In Vitro Biology
LONP1 is an AAA+ protease that maintains mitochondrial homeostasis by removing damaged or misfolded proteins. Elevated activity and expression promotes cancer cell proliferation and resistance to apoptosis-inducing reagents. Herein, we report the development of selective boronic acid-based LONP1 inhibitors using structure-based drug design as well as the first structures of human LONP1 bound to various inhibitors. Read more »
Targeting KRAS Mutant Cancers via Combination Treatment: Discovery of a 5-Fluoro-4-(3H)-quinazolinone Aryl Urea pan-RAF Kinase Inhibitor
The cover feature shows a chessboard (representative of KRAS mutant cells) and how the concerted action of the MEK inhibitor cobimetinib (rook) and the new selective pan-RAF inhibitor GNE-0749 (queen) force the opposing king (phospho-ERK, the downstream signaling node of RAF and MEK) into checkmate. Read more »
Mystery Protein Helps COVID–19 Avoid Immunity
Using the Advanced Light Source (ALS), researchers solved the structure of ORF8, a protein specific to SARS-CoV-2. Understanding the structure of ORF8 opens the door to therapy studies targeting SARS-CoV-2, the virus responsible for causing COVID-19. Read more »
To Speed Discovery, Infrared Microscopy Goes “Off the Grid”
Researchers developed a highly efficient way to collect infrared microscopy data that avoids the use of slow, grid-based raster scans. The method substantially reduces image-acquisition times by autonomously increasing sampling density in regions of interest, facilitating infrared spectromicroscopy of biochemical processes in real time. Read more »
3D Whole-Cell Mapping of Insulin Secretion
Researchers used soft x-ray tomography to gain a 3D whole-cell view of how insulin-producing pancreatic cells react upon exposure to glucose and a diabetes drug. The approach enables direct quantification of intracellular responses before, during, and after cell stimulation, providing new insights into how drugs alter cell function. Read more »