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Mass Spectrometry-Based Protein Footprinting for Protein Structure Characterization.
Acc Chem Res
January 2025
Department of Chemistry, Washington University, St. Louis, Missouri 63130, United States.
ConspectusProtein higher-order structure (HOS) is key to biological function because the mechanisms of protein machinery are encoded in protein three-dimensional structures. Mass spectrometry (MS)-based protein footprinting is advancing protein structure characterization by mapping solvent-accessible regions of proteins and changes in H-bonding, thereby providing higher order structural information. Footprinting provides insights into protein dynamics, conformational changes, and interactions, and when conducted in a differential way, can readily reveal those regions that undergo conformational change in response to perturbations such as ligand binding, mutation, thermal stress, or aggregation.
View Article and Find Full Text PDFAnalysis of the Effects of Brefeldin A on Deuterium-Labeled Sphinganine Metabolism Using Liquid Chromatography-Tandem Mass Spectrometry.
Biol Pharm Bull
January 2025
Faculty of Pharmacy and Pharmaceutical Sciences, Josai University.
Ceramide (Cer) is synthesized in the endoplasmic reticulum (ER) using sphinganine as the common backbone and is then transported to the Golgi apparatus to synthesize two complex sphingolipids, sphingomyelin (SM) and glucosylceramide (GlcCer). Brefeldin A (BFA) affects the structure of the Golgi apparatus, resulting in the redistribution of the Golgi proteins into the ER. Therefore, BFA has been used to examine the ER-to-Golgi trafficking of lipids, but the detailed lipid changes in cells upon BFA treatment are not fully understood.
View Article and Find Full Text PDFStructure resolved dynamics of type 2M Von Willebrand Disease.
J Thromb Haemost
January 2025
Division of Hematology, Departments of Internal Medicine and Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN, USA. Electronic address:
Background: Genetically determined amino acid substitutions in the platelet adhesive A1 domain alter von Willebrand factor's platelet agglutination competence resulting in both gain- (Type 2B) and loss-of-function (Type 2M) phenotypes of Von Willebrand disease. Prior studies of variants in both phenotypes revealed defects in secondary structure that altered stability and folding of the domain. An intriguing observation was that loss of function arose from both misfolding of A1 and, in a few cases, hyper-stabilization of the native structure.
View Article and Find Full Text PDFProton- and deuteron-induced cross sections on natural platinum.
Appl Radiat Isot
December 2024
Nuclear & Chemical Sciences Division, Lawrence Livermore National Laboratory, United States.
Light-ion irradiations on natural platinum were performed to measure gold-radioisotope cross sections and isotope ratios, as well as to produce a carrier-free final product. Experimental cross sections are compared to TENDL-2023. There is good agreement with this work's results and other published literature values.
View Article and Find Full Text PDFC-H Activation and Sequential Addition to Dienes and Imines: Synthesis of Amines with -Quaternary Centers and Mechanistic Studies on the Complex Interplay Between the Catalyst and Three Reactants.
ACS Catal
December 2024
Department of Chemistry, Yale University, New Haven, Connecticut 06520, United States.
A Rh(III)-catalyzed sequential C-H bond addition to dienes and in situ formed aldimines was developed, allowing for the preparation of otherwise challenging to access amines with quaternary centers at the -position. A broad range of dienes were effective inputs and installed a variety of aryl and alkyl substituents at the quaternary carbon site. Aryl and alkyl sulfonamide and carbamate nitrogen substituents were incorporated by using different formaldimine precursors.
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