4GS9: Crystal structure of the high affinity heterodimer of HIF2 alpha and ARNT C-terminal PAS domains in complex with an inactive benzoxadiazole antagonist

Hypoxia inducible factors (HIFs) are heterodimeric transcription factors induced in a variety of pathophysiological settings, including cancer. We describe the first detailed structure-activity relationship study of small molecules designed to inhibit HIF-2alpha-ARNT heterodimerization by binding an internal cavity of the HIF-2alpha PAS-B domain. Through a series of biophysical characterizations of inhibitor-protein interactions (NMR and X-ray crystallography), we have established the structural requirements for artificial inhibitors of the HIF-2alpha-ARNT PAS-B interaction. These results may serve as a foundation for discovering therapeutic agents that function by a novel mode of action.
PDB ID: 4GS9Download
MMDB ID: 108848
PDB Deposition Date: 2012/8/27
Updated in MMDB: 2018/06
Experimental Method:
x-ray diffraction
Resolution: 1.72  Å
Source Organism:
Similar Structures:
Biological Unit for 4GS9: trimeric; determined by author and by software (PISA)
Molecular Components in 4GS9
Label Count Molecule
Proteins (3 molecules)
Endothelial PAS Domain-containing Protein 1(Gene symbol: EPAS1)
Molecule annotation
Aryl Hydrocarbon Receptor Nuclear Translocator(Gene symbol: ARNT)
Molecule annotation
Chemicals (2 molecules)
* Click molecule labels to explore molecular sequence information.

Citing MMDB