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Article Dans Une Revue Nature Communications Année : 2019

Discovery of processive catalysis by an exo-hydrolase with a pocket-shaped active site

James Ketudat Cairns
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Marcel Hijnen
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Igor Tvaroška
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Ana Arda
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Jesus Jimenez-Barbero
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Mercedes Alfonso-Prieto
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Carme Rovira
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Fernanda Mendoza
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Maria Hrmova
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Résumé

Substrates associate and products dissociate from enzyme catalytic sites rapidly, which hampers investigations of their trajectories. The high-resolution structure of the native Hordeum exo-hydrolase HvExoI isolated from seedlings reveals that non-covalently trapped glucose forms a stable enzyme-product complex. Here, we report that the alkyl β-D-glucoside and methyl 6-thio-β-gentiobioside substrate analogues perfused in crystalline HvExoI bind across the catalytic site after they displace glucose, while methyl 2-thio-β-sophoroside attaches nearby. Structural analyses and multi-scale molecular modelling of nanoscale reactant movements in HvExoI reveal that upon productive binding of incoming substrates, the glucose product modifies its binding patterns and evokes the formation of a transient lateral cavity, which serves as a conduit for glucose departure to allow for the next catalytic round. This path enables substrate-product assisted processive catalysis through multiple hydrolytic events without HvExoI losing contact with oligo- or polymeric substrates. We anticipate that such enzyme plasticity could be prevalent among exo-hydrolases.
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Dates et versions

hal-02135022 , version 1 (10-06-2024)

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Victor Streltsov, Sukanya Luang, Alys Peisley, Joseph Varghese, James Ketudat Cairns, et al.. Discovery of processive catalysis by an exo-hydrolase with a pocket-shaped active site. Nature Communications, 2019, 10 (1), pp.2222. ⟨10.1038/s41467-019-09691-z⟩. ⟨hal-02135022⟩
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