Human Hydroxyacid Oxidase (HAO1)
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TEP details
Summary
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.
Structures
Structures available in TEP:
- hHAO1-FMN, bound with glyoxylate, disordered loop 4 (PDB:2NZL ): protein, ligand
- hHAO1-FMN, bound with glycolate, ordered loop 4 (PDB:6GMB ): protein, ligand
- hHAO1-FMN, bound with CCPST inhibitor (PDB:6GMC ): protein, ligand
- hHAO1-FMN, bound with fragment 2 (crystal x208) (PDB:5QIB ): protein, ligand
- hHAO1-FMN, bound with fragment 5 (crystal x368) (PDB:5QIC ): protein, ligand
- hHAO1-FMN, bound with fragment 6 (crystal x438) (PDB:5QID ): protein, ligand
- hHAO1-FMN, bound with fragment 7 (crystal x518) (PDB:5QIE ): protein, ligand
- hHAO1-FMN, bound with fragment 3 (crystal x566) (PDB:5QIF ): protein, ligand
- hHAO1-FMN, bound with fragment 4 (crystal x603) (PDB:5QIG ): protein, ligand
- hHAO1-FMN, bound with fragment 1 (crystal x604) (PDB:5QIH ): protein, ligand