Structure-Based Screening Reveals a Ligand That Stabilizes the [2Fe-2S] Clusters of Human mitoNEET and Reduces Ovarian Cancer Cell Proliferation.

Autor: Marjault HB; The Alexander Silberman Institute of Life Science and The Wolfson Centre for Applied Structural Biology, Faculty of Science and Mathematics, The Edmond J. Safra Campus at Givat Ram, The Hebrew University of Jerusalem, Jerusalem91904, Israel.; Department of Physics, RWTH Aachen University, 52074Aachen, Germany., Yang-Sung S; The Alexander Silberman Institute of Life Science and The Wolfson Centre for Applied Structural Biology, Faculty of Science and Mathematics, The Edmond J. Safra Campus at Givat Ram, The Hebrew University of Jerusalem, Jerusalem91904, Israel., Zuo K; The Alexander Silberman Institute of Life Science and The Wolfson Centre for Applied Structural Biology, Faculty of Science and Mathematics, The Edmond J. Safra Campus at Givat Ram, The Hebrew University of Jerusalem, Jerusalem91904, Israel.; Department of Physics, RWTH Aachen University, 52074Aachen, Germany., Carloni P; Department of Physics, RWTH Aachen University, 52074Aachen, Germany.; Computational Biomedicine Section, Institute of Advanced Simulation IAS-5 and Institute of Neuroscience and Medicine INM-9, Forschungszentrum Jülich GmbH, 52425Jülich, Germany.; Computational Biomedicine, Institute of Advanced Simulation IAS-5 and Institute of Neuroscience and Medicine INM-9, Forschungszentrum Jülich GmbH, 52425Jülich, Germany.; JARA Institute: Molecular Neuroscience and Imaging, Institute of Neuroscience and Medicine INM-11, Forschungszentrum Jülich GmbH, 52425Jülich, Germany., Mittler R; Department of Surgery, University of Missouri School of Medicine, and Interdisciplinary Plant Group, Christopher S. Bond Life Sciences Center, University of Missouri, 1201 Rollins Street, Columbia, Missouri65211, United States., Nechushtai R; The Alexander Silberman Institute of Life Science and The Wolfson Centre for Applied Structural Biology, Faculty of Science and Mathematics, The Edmond J. Safra Campus at Givat Ram, The Hebrew University of Jerusalem, Jerusalem91904, Israel.
Jazyk: angličtina
Zdroj: The journal of physical chemistry. B [J Phys Chem B] 2022 Nov 24; Vol. 126 (46), pp. 9559-9565. Date of Electronic Publication: 2022 Nov 14.
DOI: 10.1021/acs.jpcb.2c05728
Abstrakt: Human NEET proteins play an important role in a variety of diseases, including cancer. Using the recently published X-ray structure of the human mNT-M1 complex, we screened a commercial chemical compound library and identified a new human mitoNEET (mNT) binding ligand (NTS-01). Biochemical investigations revealed that NTS-01 specifically binds to the human mNT protein and stabilizes its [2Fe-2S] clusters under oxidative conditions in vitro . Treatment of ovarian cancer cells with NTS-01 induces ovarian cancer (SKOV-3) mitochondrial fragmentation (fission) and reduces ovarian cancer cell proliferation in a 2D single-layer cell culture, as well as in a 3D-spheroids culture. The NTS-01 molecule represents therefore a new lead compound for further drug design studies attempting to develop efficient treatment against ovarian cancer.
Databáze: MEDLINE