6Z1H

Ancestral glycosidase (family 1)

6Z1H の概要

• エントリーDOI: 10.2210/pdb6z1h/pdb
• 関連するPDBエントリー: 6Z1M
• 分子名称: ANCESTRAL RECONSTRUCTED GLYCOSIDASE, Residues 249 to 266 of chain A and 246 to 258 of chain B could not be identified and has been included as UNK in chain C and D, respectively., GLYCEROL, ... (7 entities in total)
• 機能のキーワード: ancestral reconstructed, glycosidase, family 1, hydrolase
• 由来する生物種: synthetic construct; 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 108235.84

構造登録者

Gavira, J.A.,Risso, V.A.,Sanchez-Ruiz, J.M.,Gamiz-Arco, G.,Gutierrez-Rus, L.,Ibarra-Molero, B.,Hoshino, Y.,Petrovic, D.,Romero-Rivera, A.,Seelig, B.,Kamerlin, S.C.L.,Gaucher, E.A. (登録日: 2020-05-13, 公開日: 2020-07-22, 最終更新日: 2024-01-24)

主引用文献

Gamiz-Arco, G.,Gutierrez-Rus, L.I.,Risso, V.A.,Ibarra-Molero, B.,Hoshino, Y.,Petrovic, D.,Justicia, J.,Cuerva, J.M.,Romero-Rivera, A.,Seelig, B.,Gavira, J.A.,Kamerlin, S.C.L.,Gaucher, E.A.,Sanchez-Ruiz, J.M.
Heme-binding enables allosteric modulation in an ancient TIM-barrel glycosidase.
Nat Commun, 12:380-380, 2021

PubMed Abstract: 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.

PubMed: 33452262
DOI: 10.1038/s41467-020-20630-1

実験手法

X-RAY DIFFRACTION (2.5 Å)