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Abstract Electrospray deposition of copper salt‐containing microdroplets onto the liquid surface of an electrically grounded reaction mixture leads to the formation of Cu nanoclusters, which then catalyze the azide‐alkyne cycloaddition (AAC) reaction to form triazoles. This method of in situ nanocatalyst preparation provided 17 times higher catalytic activity compared to that in the conventional catalytic reaction. The gentle landing of the Cu‐containing droplets onto the liquid surface forms a thin film of catalyst which promotes the heterogeneous AAC reaction while showing diffusion‐controlled kinetics. UV‐vis spectral characterization confirms that the catalyst is comprised of Cu nanoclusters. This unique catalytic strategy was validated using several substrates and the corresponding products were confirmed by tandem mass spectrometry (MS/MS) analysis.
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Filament formation drives catalysis by glutaminase enzymes important in cancer progression
Abstract The glutaminase enzymes GAC and GLS2 catalyze the hydrolysis of glutamine to glutamate, satisfying the ‘glutamine addiction’ of cancer cells. They are the targets of anti-cancer drugs; however, their mechanisms of activation and catalytic activity have been unclear. Here we demonstrate that the ability of GAC and GLS2 to form filaments is directly coupled to their catalytic activity and present their cryo-EM structures which provide a view of the conformational states essential for catalysis. Filament formation guides an ‘activation loop’ to assume a specific conformation that works together with a ‘lid’ to close over the active site and position glutamine for nucleophilic attack by an essential serine. Our findings highlight how ankyrin repeats on GLS2 regulate enzymatic activity, while allosteric activators stabilize, and clinically relevant inhibitors block, filament formation that enables glutaminases to catalyze glutaminolysis and support cancer progression.
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- Award ID(s):
- 1719875
- PAR ID:
- 10494015
- Publisher / Repository:
- Nature Publishing Group
- Date Published:
- Journal Name:
- Nature Communications
- Volume:
- 15
- Issue:
- 1
- ISSN:
- 2041-1723
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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