The fabrication and testing of a prototype deep-depletion direct-conversion X-ray CCD detector are described. The device is fabricated on 600 µm-thick high-resistivity silicon, with 24 × 24 µm pixels in a 4k × 4k pixel format. Calibration measurements and the results of initial protein crystallography experiments at the Cornell High Energy Synchrotron Source (CHESS) F1 beamline are described, as well as suggested improvements for future versions of the detector.
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http://dx.doi.org/10.1107/S0021889813016592 | DOI Listing |
J Clin Invest
January 2025
Department of Biomedical Engineering, Columbia University, New York, New York, USA.
Loss of Bcl2-associated athanogene 3 (BAG3) is associated with dilated cardiomyopathy (DCM). BAG3 regulates sarcomere protein turnover in cardiomyocytes; however, the function of BAG3 in other cardiac cell types is understudied. In this study, we used an isogenic pair of BAG3-knockout and wild-type human induced pluripotent stem cells (hiPSCs) to interrogate the role of BAG3 in hiPSC-derived cardiac fibroblasts (CFs).
View Article and Find Full Text PDFJ Phys Chem Lett
December 2024
Molecular Ocean Lab, Institute for Advanced Chemistry of Catalonia, IQAC-CSIC, Carrer de Jordi Girona 18-26, 08034 Barcelona, Spain.
Protein-bound ligands can adopt a range of different conformations, collectively defining a ligand envelope that has proven to be crucial for the design of potent and selective drugs. Yet, the cryptic nature of this ligand envelope makes it difficult to visualize, characterize, and ultimately exploit for drug design. Using enhanced molecular dynamics simulations, here, we provide a general framework to reconstruct the cryptic ligand envelope that is dynamically accessible by protein-bound small molecules in solution.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
January 2025
Department of Chemistry, Duke University, Durham, NC 27708.
Invasive fungal infections are a leading cause of death worldwide. Translating molecular insights into clinical benefits is challenging because fungal pathogens and their hosts share similar eukaryotic physiology. Consequently, current antifungal treatments have limited efficacy, may be poorly fungicidal in the host, can exhibit toxicity, and are increasingly compromised by emerging resistance.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
January 2025
Department of Chemistry and Biochemistry, University of California, Los Angeles, CA 90095.
To successfully mount infections, nearly all bacterial pathogens must acquire iron, a key metal cofactor that primarily resides within human hemoglobin. causes the life-threatening respiratory disease diphtheria and captures hemoglobin for iron scavenging using the surface-displayed receptor HbpA. Here, we show using X-ray crystallography, NMR, and in situ binding measurements that selectively captures iron-loaded hemoglobin by partially ensconcing the heme molecules of its α subunits.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
January 2025
Department of Biochemistry, Brandeis University, Waltham, MA 02454.
Reversible protein phosphorylation directs essential cellular processes including cell division, cell growth, cell death, inflammation, and differentiation. Because protein phosphorylation drives diverse diseases, kinases and phosphatases have been targets for drug discovery, with some achieving remarkable clinical success. Most protein kinases are activated by phosphorylation of their activation loops, which shifts the conformational equilibrium of the kinase toward the active state.
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