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Structural analysis of extracellular ATP-independent chaperones of streptococcal species and protein substrate interactions.
mSphere
January 2025
Department of Biological Sciences, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Unlabelled: During infection, bacterial pathogens rely on secreted virulence factors to manipulate the host cell. However, in gram-positive bacteria, the molecular mechanisms underlying the folding and activity of these virulence factors after membrane translocation are not clear. Here, we solved the protein structures of two secreted parvulin and two secreted cyclophilin-like peptidyl-prolyl isomerase (PPIase) ATP-independent chaperones found in gram-positive streptococcal species.
View Article and Find Full Text PDFPractical management of adverse events in patients receiving tarlatamab, a delta-like ligand 3-targeted bispecific T-cell engager immunotherapy, for previously treated small cell lung cancer.
Cancer
February 2025
University of Maryland Marlene and Stewart Greenebaum Comprehensive Cancer Center, University of Maryland Medical Center, Baltimore, Maryland, USA.
Tarlatamab is a bispecific T-cell engager immunotherapy targeting delta-like ligand 3 (DLL3) and the cluster of differentiation 3 (CD3) molecule. In the phase 2 DeLLphi-301 trial of tarlatamab for patients with previously treated small cell lung cancer, tarlatamab 10 mg every 2 weeks achieved durable responses and encouraging survival outcomes. Analyses of updated safety data from the DeLLphi-301 trial demonstrated that the most common treatment-emergent adverse events were cytokine release syndrome (53%), pyrexia (38%), decreased appetite (36%), dysgeusia (32%), and an emia (30%).
View Article and Find Full Text PDFDirected Evolution's Selective Use of Quantum Tunneling in Designed Enzymes─A Combined Theoretical and Experimental Study.
J Phys Chem B
January 2025
Department of Chemistry and Biochemistry, University of Arizona, 1306 East University Boulevard, Tucson, Arizona 85721, United States.
Natural enzymes are powerful catalysts, reducing the apparent activation energy for reactions and enabling chemistry to proceed as much as 10 times faster than the corresponding solution reaction. It has been suggested for some time that, in some cases, quantum tunneling can contribute to this rate enhancement by offering pathways through a barrier inaccessible to activated events. A central question of interest to both physical chemists and biochemists is the extent to which evolution introduces mechanisms below the barrier, or tunneling mechanisms.
View Article and Find Full Text PDFCatalyst-Controlled, Site-Selective Functionalization of Levoglucosan Analogues Mediated by Chiral Zinc Diamine Complexes.
J Org Chem
January 2025
Département de Chimie, 1045 av. De la Médecine, Université Laval, Québec City, Quebec G1 V 0A6, Canada.
In this work, we developed a site-selective functionalization of levoglucosan analogues. This strategy used simple zinc diamine complexes for regioselective functionalization at O2 or O4. Successful transformations of monotosyl analogues allowed the preparation of useful intermediates in carbohydrate chemistry, such as four protected Černý epoxides and three protected amino sugars.
View Article and Find Full Text PDFDevelopment of translationally active cell lysates from different filamentous fungi for application in cell-free protein synthesis.
Enzyme Microb Technol
January 2025
Institute of Biotechnology, Brandenburg University of Technology Cottbus-Senftenberg, Universitätsplatz 1, Senftenberg 01968, Germany. Electronic address:
There is an enormous potential for cell-free protein synthesis (CFPS) systems based on filamentous fungi in view of their simple, fast and mostly inexpensive cultivation with high biomass space-time yields and in view of their catalytic capacity. In 12 of the 22 different filamentous fungi examined, in vitro translation of at least one of the two reporter proteins GFP and firefly luciferase was detected. The lysates showing translation of a reporter protein usually were able to synthesize a functional cell-free expressed unspecific peroxygenase (UPO) from the basidiomycete Cyclocybe (Agrocybe) aegerita.
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