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Dataset Open Access

Human Hydroxyacid Oxidase (HAO1); A Target Enabling Package

Sabrina MacKinnon; Gustavo Arruda Bezerra; Tobias Krojer; Anthony R. Bradley; Romain Talon; Jose Brandao-Neto; Alice Douangamath; Udo Oppermann; Frank von Delft; Paul E. Brennan; Wyatt W. Yue

This project provides the tools and data to develop small molecule inhibitors for an inherited metabolic disorder (Primary hyperoxaluria type 1) due to the defective enzyme (AGXT), by targeting the enzyme (HAO1) upstream of the glyoxylate metabolic pathway to mitigate the defect (i.e. substrate reduction approach). This TEP package includes recombinant human HAO1 purification protocols, structures of the HAO1 in different states, in vitro assays to detect ligand/inhibitor binding (DSF, SPR) and enzyme activity (amplex red assay) of human HAO1, as well as initial chemical matters identified from crystallography-based fragment screening.

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