Structural highlights
Disease
CATA_HUMAN Defects in CAT are the cause of acatalasemia (ACATLAS) [MIM:614097. A metabolic disorder characterized by absence of catalase activity in red cells and is often associated with ulcerating oral lesions.[1]
Function
CATA_HUMAN Occurs in almost all aerobically respiring organisms and serves to protect cells from the toxic effects of hydrogen peroxide. Promotes growth of cells including T-cells, B-cells, myeloid leukemia cells, melanoma cells, mastocytoma cells and normal and transformed fibroblast cells.[2]
Publication Abstract from PubMed
Catalase (CAT) is an important antioxidant enzyme that breaks down H(2)O(2) into water and oxygen. Inhibitor-modulating CAT activity in cancer cells is emerging as a potential anticancer strategy. However, the discovery of CAT inhibitors towards the heme active center located at the bottom of long and narrow channel has made little progress. Therefore, targeting new binding site is of great importance for the development of efficient CAT inhibitors. Here, the first NADPH-binding site inhibitor of CAT, BT-Br, was designed and synthesized successfully. The cocrystal structure of BT-Br-bound CAT complex was determined with a resolution of 2.2 A (PDB ID:8HID), which showed clearly that BT-Br bound at the NADPH-binding site. Furthermore, BT-Br was demonstrated to induce ferroptosis in castration-resistant prostate cancer (CRPC) DU145 cells and eventually reduce CRPC tumors in vivo effectively. The work indicates that CAT has potential as a novel target for CRPC therapy based on ferroptosis inducing.
A catalase inhibitor: Targeting the NADPH-binding site for castration-resistant prostate cancer therapy.,Cao YY, Chen YY, Wang MS, Tong JJ, Xu M, Zhao C, Lin HY, Mei LC, Dong J, Zhang WL, Qin YX, Huang W, Zhang D, Yang GF Redox Biol. 2023 Jul;63:102751. doi: 10.1016/j.redox.2023.102751. Epub 2023 May , 16. PMID:37216701[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Wen JK, Osumi T, Hashimoto T, Ogata M. Molecular analysis of human acatalasemia. Identification of a splicing mutation. J Mol Biol. 1990 Jan 20;211(2):383-93. PMID:2308162 doi:http://dx.doi.org/10.1016/0022-2836(90)90359-T
- ↑ Takeuchi A, Miyamoto T, Yamaji K, Masuho Y, Hayashi M, Hayashi H, Onozaki K. A human erythrocyte-derived growth-promoting factor with a wide target cell spectrum: identification as catalase. Cancer Res. 1995 Apr 1;55(7):1586-9. PMID:7882369
- ↑ Cao YY, Chen YY, Wang MS, Tong JJ, Xu M, Zhao C, Lin HY, Mei LC, Dong J, Zhang WL, Qin YX, Huang W, Zhang D, Yang GF. A catalase inhibitor: Targeting the NADPH-binding site for castration-resistant prostate cancer therapy. Redox Biol. 2023 Jul;63:102751. PMID:37216701 doi:10.1016/j.redox.2023.102751
