Heme-binding enables allosteric modulation in an ancient TIM-barrel glycosidase
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Gámiz Arco, María Gloria; Gutiérrez Rus, Luis Ignacio; Alejandra Risso, Valeria; Ibarra Molero, Beatriz; Justicia Ladrón De Guevara, JoséEditorial
Nature Research
Date
2021-01-15Referencia bibliográfica
Gamiz-Arco, G., Gutierrez-Rus, L. I., Risso, V. A., Ibarra-Molero, B., Hoshino, Y., Petrović, D., ... & Sanchez-Ruiz, J. M. (2021). Heme-binding enables allosteric modulation in an ancient TIM-barrel glycosidase. Nature communications, 12(1), 1-16. [https://doi.org/10.1038/s41467-020-20630-1]
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Uppsala UniversityAbstract
Glycosidases are phylogenetically widely distributed enzymes that are crucial for the cleavage
of glycosidic bonds. Here, we present the exceptional properties of a putative ancestor
of bacterial and eukaryotic family-1 glycosidases. The ancestral protein shares the TIM-barrel
fold with its modern descendants but displays large regions with greatly enhanced conformational
flexibility. Yet, the barrel core remains comparatively rigid and the ancestral
glycosidase activity is stable, with an optimum temperature within the experimental range for
thermophilic family-1 glycosidases. None of the ∼5500 reported crystallographic structures
of ∼1400 modern glycosidases show a bound porphyrin. Remarkably, the ancestral glycosidase
binds heme tightly and stoichiometrically at a well-defined buried site. Heme binding
rigidifies this TIM-barrel and allosterically enhances catalysis. Our work demonstrates the
capability of ancestral protein reconstructions to reveal valuable but unexpected biomolecular
features when sampling distant sequence space. The potential of the ancestral glycosidase as
a scaffold for custom catalysis and biosensor engineering is discussed.