SNAP output for PDB entry 6vgg [SNAP web server]

PDB-id

6vgg; SNAP-derived features in text and JSON formats; DNAproDB

Class

transcription

Method

X-ray (4.31 Å)

Summary

Crystal structure of the DNA binding domains of human transcription factor erg, human runx2 bound to core binding factor beta (cbfb), and mithramycin, in complex with 16mer DNA cagaggatgtggcttc

Reference

Hou C, Mandal A, Rohr J, Tsodikov OV (2021): "Allosteric interference in oncogenic FLI1 and ERG transactions by mithramycins." Structure, 29, 404-412.e4. doi: 10.1016/j.str.2020.11.012.

Abstract

ETS family transcription factors of ERG and FLI1 play a key role in oncogenesis of prostate cancer and Ewing sarcoma by binding regulatory DNA sites and interfering with function of other factors. Mithramycin (MTM) is an anti-cancer, DNA binding natural product that functions as a potent antagonist of ERG and FLI1 by an unknown mechanism. We present a series of crystal structures of the DNA binding domain (DBD) of ERG/FLI1 culminating in a structure of a high-order complex of the ERG/FLI1 DBD, transcription factor Runx2, core-binding factor beta (Cbfβ), and MTM on a DNA enhancer site, along with supporting DNA binding studies using MTM and its analogues. Taken together, these data provide insight into allosteric mechanisms underlying ERG and FLI1 transactions and their disruption by MTM analogues.