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. 2021 Jan 28;8:630888. doi: 10.3389/fchem.2020.630888

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Copyright © 2021 Bijlmakers.

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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Differences at the TAK-243 binding site between human and trypanosomatid UBA1s. (A) The crystal structure of S. cerevisiae UBA1 complexed with a TAK-243-ubiquitin adduct (PDB: 5L6J). (B) chemical structure of TAK-243. (C) Detailed view of the TAK-243 binding site in which the crucial differences with the T. brucei TbUBA1s are labeled. (D) Amino acid sequence comparison of human, yeast and trypanosomatid UBA1s. The residues that contribute to the resistance of TbUBA1a and TbUBA1b to TAK-243 are indicated with arrows.