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

Henri Baptiste Marjault, Sohn Yang-Sung, Ke Zuo, Paolo Carloni, Ron Mittler, Rachel Nechushtai*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

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.

Original languageAmerican English
Pages (from-to)9559-9565
Number of pages7
JournalJournal of Physical Chemistry B
Volume126
Issue number46
DOIs
StatePublished - 24 Nov 2022

Bibliographical note

Funding Information:
H.-B.M. and K.Z. were supported by the Marie Skłodowska-Curie grant agreement No. 765048. The confocal images were collected in the microscopy center from the Charles E. Smith Family and the Prof. Joel Elkes Laboratory for Collaborative Research in Psychology.

Publisher Copyright:
© 2022 American Chemical Society.

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