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, Maria Hrmova

Research output: Contribution to journalArticleResearch

2 Citations (Scopus)

Abstract

© 2019, Crown. 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.
Original languageEnglish
Article number2222
JournalNature Communications
Volume10
DOIs
Publication statusPublished - 1 Dec 2019

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