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

Victor A. Streltsov, Sukanya Luang, Alys Peisley, Joseph N. Varghese, James R. Ketudat Cairns, Sebastien Fort, Marcel Hijnen, Igor Tvaroška, Ana Ardá, Jesús Jiménez-Barbero, Mercedes Alfonso-Prieto, Carme Rovira, Fernanda Mendoza, Laura Tiessler-Sala, José-Emilio Sánchez-Aparicio, Jaime Rodríguez-Guerra, José M. Lluch, Jean-Didier Maréchal, Laura Masgrau and Maria Hrmova ()
Additional contact information
Victor A. Streltsov: Materials Science and Engineering
Sukanya Luang: University of Adelaide, Waite Campus
Alys Peisley: Materials Science and Engineering
Joseph N. Varghese: Materials Science and Engineering
James R. Ketudat Cairns: Suranaree University of Technology
Sebastien Fort: Centre de Recherches sur les Macromolécules Végétales
Marcel Hijnen: GE Healthcare Life Sciences
Igor Tvaroška: Slovak Academy of Sciences
Ana Ardá: Centre for Cooperative Research in Biosciences
Jesús Jiménez-Barbero: Centre for Cooperative Research in Biosciences
Mercedes Alfonso-Prieto: Universitat de Barcelona
Carme Rovira: Universitat de Barcelona
Fernanda Mendoza: Universidad Andrés Bello, Sede Concepción
Laura Tiessler-Sala: Universitat Autònoma de Barcelona
José-Emilio Sánchez-Aparicio: Universitat Autònoma de Barcelona
Jaime Rodríguez-Guerra: Universitat Autònoma de Barcelona
José M. Lluch: Universitat Autònoma de Barcelona
Jean-Didier Maréchal: Universitat Autònoma de Barcelona
Laura Masgrau: Universitat Autònoma de Barcelona
Maria Hrmova: University of Adelaide, Waite Campus

Nature Communications, 2019, vol. 10, issue 1, 1-17

Abstract: Abstract 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.

Date: 2019
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DOI: 10.1038/s41467-019-09691-z

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