Swapping Interface Contacts in the Homodimeric tRNA-Guanine Transglycosylase: An Option for Functional Regulation - Archive ouverte HAL
Article Dans Une Revue Angewandte Chemie International Edition Année : 2018

Swapping Interface Contacts in the Homodimeric tRNA-Guanine Transglycosylase: An Option for Functional Regulation

Résumé

The enzyme tRNA‐guanine transglycosylase, a target to fight Shigellosis, recognizes tRNA only as a homodimer and performs full nucleobase exchange at the wobble position. Active‐site inhibitors block the enzyme function by competitively replacing tRNA. In solution, the wild‐type homodimer dissociates only marginally, whereas mutated variants show substantial monomerization in solution. Surprisingly, one inhibitor transforms the protein into a twisted state, whereby one monomer unit rotates by approximately 130°. In this altered geometry, the enzyme is no longer capable of binding and processing tRNA. Three sugar‐type inhibitors have been designed and synthesized, which bind to the protein in either the functionally competent or twisted inactive state. They crystallize with the enzyme side‐by‐side under identical conditions from the same crystallization well. Possibly, the twisted inactive form corresponds to a resting state of the enzyme, important for its functional regulation.

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Chimie
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Dates et versions

hal-02341508 , version 1 (31-10-2019)

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Citer

Frederik Rainer Ehrmann, Jorna Kalim, Toni Pfaffeneder, Bruno Bernet, Christoph Hohn, et al.. Swapping Interface Contacts in the Homodimeric tRNA-Guanine Transglycosylase: An Option for Functional Regulation. Angewandte Chemie International Edition, 2018, 57 (32), pp.10085-10090. ⟨10.1002/anie.201804627⟩. ⟨hal-02341508⟩
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