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http://dx.doi.org/10.1038/newbio234005a0 | DOI Listing |
bioRxiv
January 2025
Ben-May Institute for Cancer Research, The University of Chicago, 929 East 57th Street, Chicago, Illinois 60637, USA.
Insulin degrading enzyme (IDE) is a dimeric 110 kDa M16A zinc metalloprotease that degrades amyloidogenic peptides diverse in shape and sequence, including insulin, amylin, and amyloid-β, to prevent toxic amyloid fibril formation. IDE has a hollow catalytic chamber formed by four homologous subdomains organized into two ~55 kDa N- and C- domains (IDE-N and IDE-C, respectively), in which peptides bind, unfold, and are repositioned for proteolysis. IDE is known to transition between a closed state, poised for catalysis, and an open state, able to release cleavage products and bind new substrate.
View Article and Find Full Text PDFChemMedChem
January 2025
CBS: Centre de Biologie Structurale, ABCIS, 29 rue de Navacelles, 34090, Montpellier, FRANCE.
Aminoglycoside-phosphotransferases (APHs) are a class of bacterial enzymes that mediate acquired resistance to aminoglycoside antibiotics. Here we report the identification of small molecules counteracting aminoglycoside resistance in Enterococcus casseliflavus. Molecular dynamics simulations were performed to identify an allosteric pocket in three APH enzymes belonging to 3' and 2'' subfamilies in which we then screened, in silico, 12,000 small molecules.
View Article and Find Full Text PDFNat Commun
January 2025
Department of Plant Molecular Biology and Physiology, Albrecht-von-Haller Institute for Plant Sciences, Georg-August-University Göttingen, Julia-Lermontowa-Weg 3, 37077, Göttingen, Germany.
Class I glutaredoxins (GRXs) are nearly ubiquitous proteins that catalyse the glutathione (GSH)-dependent reduction of mainly glutathionylated substrates. In land plants, a third class of GRXs has evolved (class III). Class III GRXs regulate the activity of TGA transcription factors through yet unexplored mechanisms.
View Article and Find Full Text PDFMolecules
December 2024
Chengdu Institute of Biology, Chinese Academy of Sciences, Chengdu 610041, China.
Ligand fishing is a promising strategy for the screening of active ingredients from complex natural products. In this work, human tyrosinase (hTYR) was displayed on the surface of Chinese hamster ovary (CHO) cells for the first time; it was then used as bait to develop a new method for ligand fishing. The localization of hTYR on the CHO cell surface was verified by an enzyme activity test and fluorescence microscopy.
View Article and Find Full Text PDFPlanta
January 2025
Key Laboratory of Chemical Biology of Natural Products, Ministry of Education, School of Pharmaceutical Sciences, Shandong University, Jinan, 250012, Shandong, China.
The evolutionary conservation of type III polyketide synthases (PKS) in Selaginella has been elucidated, and the critical amino acid residues of the anther-specific chalcone synthase-like enzyme (SmASCL) have been identified. Selaginella species are the oldest known vascular plants and a valuable resource for the study of metabolic evolution in land plants. Polyketides, especially flavonoids and sporopollenin precursors, are essential prerequisites for plant land colonization.
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