8J2U

Glucosyl Transferase NbUGT72AY1 co-crystallized with UDP

Summary for 8J2U

• Entry DOI: 10.2210/pdb8j2u/pdb
• Related: 8J2T
• Descriptor: Glycosyltransferase, URIDINE-5'-DIPHOSPHATE (2 entities in total)
• Functional Keywords: glucosyl transferase, transferase
• Biological source: Nicotiana tabacum (common tobacco)
• Total number of polymer chains: 2
• Total formula weight: 107877.29

Authors

Arold, S.T.,Hameed, U.F.S. (deposition date: 2023-04-15, release date: 2024-04-17, Last modification date: 2025-04-09)

Primary citation

Liao, J.,Shahul Hameed, U.F.,Hoffmann, T.D.,Kurze, E.,Sun, G.,Steinchen, W.,Nicoli, A.,Di Pizio, A.,Kuttler, C.,Song, C.,Catici, D.A.M.,Assaad-Gerbert, F.,Hoffmann, T.,Arold, S.T.,Schwab, W.G.
beta-Carotene alleviates substrate inhibition caused by asymmetric cooperativity.
Nat Commun, 16:3065-3065, 2025

PubMed Abstract: Enzymes are essential catalysts in biological systems. Substrate inhibition, once dismissed, is now observed in 20% of enzymes and is attributed to the formation of an unproductive enzyme-substrate complex, with no structural evidence of unproductivity provided to date. This study uncovers the molecular mechanism of substrate inhibition in tobacco glucosyltransferase NbUGT72AY1, which transfers glucose to phenols for plant protection. The peculiarity that β-carotene strongly attenuates the substrate inhibition of NbUGT72AY1, despite being a competitive inhibitor, allows to determine the conformational changes that occur during substrate binding in both active and substrate-inhibited complexes. Crystallography reveals structurally different ternary enzyme-substrate complexes that do not conform to classical mechanisms. An alternative pathway suggests substrates bind randomly, but the reaction occurs only if a specific order is followed (asymmetric cooperativity). This unreported paradigm explains substrate inhibition and reactivation by competitive inhibitors, opening new research avenues in metabolic regulation and industrial applications.

PubMed: 40157902
DOI: 10.1038/s41467-025-58259-7

Experimental method

X-RAY DIFFRACTION (3.32 Å)