We report herein a novel phosphopeptide microarray capable of noncovalently "trapping" catalytically inactive mutants of protein tyrosine phosphatases (PTPs), and its application in high-throughput determination of PTP substrate specificity.
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Nat 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
School of Chemical Sciences, University of Chinese Academy of Sciences, No. 19A, Yuquan Road, Beijing 100049, China.
The src-homology 2 domain-containing phosphatase 2 (SHP2) is a human cytoplasmic protein tyrosine phosphatase that plays a crucial role in cellular signal transduction. Aberrant activation and mutations of SHP2 are associated with tumor growth and immune suppression, thus making it a potential target for cancer therapy. Initially, researchers sought to develop inhibitors targeting SHP2's catalytic site (protein tyrosine phosphatase domain, PTP).
View Article and Find Full Text PDFJ Chem Inf Model
January 2025
Cancer Innovation Laboratory, National Cancer Institute, Frederick, Maryland 21702, United States.
mTOR plays a crucial role in PI3K/AKT/mTOR signaling. We hypothesized that mTOR activation mechanisms driving oncogenesis can advise effective therapeutic designs. To test this, we combined cancer genomic analysis with extensive molecular dynamics simulations of mTOR oncogenic variants.
View Article and Find Full Text PDFNature
January 2025
Institut für Biochemie, Albert-Ludwigs-Universität Freiburg, Freiburg im Breisgau, Germany.
The oxygen-sensitive molybdenum-dependent nitrogenase of Azotobacter vinelandii is protected from oxidative damage by a reversible 'switch-off' mechanism. It forms a complex with a small ferredoxin, FeSII (ref. ) or the 'Shethna protein II', which acts as an O sensor and associates with the two component proteins of nitrogenase when its [2Fe:2S] cluster becomes oxidized.
View Article and Find Full Text PDFNature
January 2025
Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA, USA.
The low reduction potentials required for the reduction of dinitrogen (N) render metal-based nitrogen-fixation catalysts vulnerable to irreversible damage by dioxygen (O). Such O sensitivity represents a major conundrum for the enzyme nitrogenase, as a large fraction of nitrogen-fixing organisms are either obligate aerobes or closely associated with O-respiring organisms to support the high energy demand of catalytic N reduction. To counter O damage to nitrogenase, diazotrophs use O scavengers, exploit compartmentalization or maintain high respiration rates to minimize intracellular O concentrations.
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