Mechanistic insights into glycoside 3-oxidases involved in C -glycoside metabolism in soil microorganisms
Taborda, André (Universidade Nova de Lisboa)
Frazão, Tomás (Universidade Nova de Lisboa)
Rodrigues, Miguel V. (Universidade Nova de Lisboa)
Fernández-Luengo Flores, Xavier (Universitat Autònoma de Barcelona. Departament de Química)
Sancho, Ferran (Zymvol Biomodeling)
Lucas, Maria Fátima (Zymvol Biomodeling)
Frazão, Carlos (Universidade Nova de Lisboa)
Melo, Eduardo P. (Universidade do Algarve)
Ventura, M. Rita (Universidade Nova de Lisboa)
Masgrau, Laura (Universitat Autònoma de Barcelona. Departament de Química)
Borges, Patrícia T. (Universidade Nova de Lisboa)
Martins, Lígia O. (Universidade Nova de Lisboa)

Data:	2023
Resum:	C-glycosides are natural products with important biological activities but are recalcitrant to degradation. Glycoside 3-oxidases (G3Oxs) are recently identified bacterial flavo-oxidases from the glucose-methanol-coline (GMC) superfamily that catalyze the oxidation of C-glycosides with the concomitant reduction of O2 to H2O2. This oxidation is followed by C-C acid/base-assisted bond cleavage in two-step C-deglycosylation pathways. Soil and gut microorganisms have different oxidative enzymes, but the details of their catalytic mechanisms are largely unknown. Here, we report that PsG3Ox oxidizes at 50,000-fold higher specificity (kcat/Km) the glucose moiety of mangiferin to 3-keto-mangiferin than free D-glucose to 2-keto-glucose. Analysis of PsG3Ox X-ray crystal structures and PsG3Ox in complex with glucose and mangiferin, combined with mutagenesis and molecular dynamics simulations, reveal distinctive features in the topology surrounding the active site that favor catalytically competent conformational states suitable for recognition, stabilization, and oxidation of the glucose moiety of mangiferin. Furthermore, their distinction to pyranose 2-oxidases (P2Oxs) involved in wood decay and recycling is discussed from an evolutionary, structural, and functional viewpoint.
Ajuts:	European Commission PID2021-126897NB-I00 European Commission PRE2019-088412 European Commission 824017
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Enzyme mechanisms ; Metabolic pathways ; X-ray crystallography
Publicat a:	Nature communications, Vol. 14 (November 2023) , art. 7289, ISSN 2041-1723

DOI: 10.1038/s41467-023-42000-3
PMID: 37963862

17 p, 3.1 MB

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