9HXV

Crystal structure of TET2-DNA in complex with IOX1

Summary for 9HXV

• Entry DOI: 10.2210/pdb9hxv/pdb
• Descriptor: Methylcytosine dioxygenase TET2, 12mer-DNA, FE (II) ION, ... (8 entities in total)
• Functional Keywords: iox1, tet2, oxidoreductase
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 3
• Total formula weight: 59793.49

Authors

Niggenaber, J.,Mueller, M.P.,Rauh, D. (deposition date: 2025-01-08, release date: 2025-04-09, Last modification date: 2025-05-28)

Primary citation

Willems, S.,Maksumic, L.,Niggenaber, J.,Lin, T.C.,Schulz, T.,Weisner, J.,Sievers, S.,Muller, M.P.,Summerer, D.,Rauh, D.
Advancing TET Inhibitor Development: From Structural Insights to Biological Evaluation.
Acs Med.Chem.Lett., 16:804-810, 2025

PubMed Abstract: Ten-eleven translocation (TET) methylcytosine dioxygenases are part of the epigenetic regulatory machinery that erases DNA methylation. Aberrant TET activities are frequently found in hematopoietic malignancies, where loss of TET2 function leads to DNA hypermethylation. A comprehensive understanding of the biological role of TETs is essential to elucidate disease pathogenesis and identify novel therapeutic strategies. We present a robust pipeline integrating protein X-ray crystallography, molecular modeling, and pharmacophore analysis to advance the current TET inhibitor development. In addition, we have synthesized and evaluated a series of 8-hydroxyquinoline (8-HQ) derivatives, demonstrating their potential as chemical tools to explore TET function further. These findings lay the groundwork for a TET-centered therapeutic approach.

PubMed: 40365382
DOI: 10.1021/acsmedchemlett.5c00042

Experimental method

X-RAY DIFFRACTION (1.9 Å)