SNAP-annotated 5mC-DNA-protein interactions: PDB entry 9hxv

PDB-id

9hxv; DSSR-derived features in text and JSON formats; DNAproDB

Class

oxidoreductase

Method

X-ray (1.9 Å)

Summary

Crystal structure of tet2-DNA in complex with iox1

Reference

Willems S, Maksumic L, Niggenaber J, Lin TC, Schulz T, Weisner J, Sievers S, Muller MP, Summerer D, Rauh D (2025): "Advancing TET Inhibitor Development: From Structural Insights to Biological Evaluation." Acs Med.Chem.Lett., 16, 804-810. doi: 10.1021/acsmedchemlett.5c00042.

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.

• The contacts include paired nucleotides (mostly a G in Watson-Crick G-C pairing) and amino-acids within a 4.5-Å distance cutoff to base atoms of 5mC.
• The structure is oriented in the base reference frame of 5mC, allowing for easy comparison and direct superimposition between entries.
• The black sphere (•) denotes the 5-methyl carbon atom in 5mC.