2P7A

Crystal Structure of Estrogen Related Receptor g in complex with 3-methyl phenol

2P7A の概要

• エントリーDOI: 10.2210/pdb2p7a/pdb
• 関連するPDBエントリー: 2p7g 2p7z
• 分子名称: Estrogen-related receptor gamma, 4-CHLORO-3-METHYLPHENOL (3 entities in total)
• 機能のキーワード: three layered alpha helical sandwich, hormone receptor
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Nucleus : P62508
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 28529.52

構造登録者

Abad, M.C. (登録日: 2007-03-20, 公開日: 2008-02-26, 最終更新日: 2024-04-03)

主引用文献

Abad, M.C.,Askari, H.,O'Neill, J.,Klinger, A.L.,Milligan, C.,Lewandowski, F.,Springer, B.,Spurlino, J.,Rentzeperis, D.
Structural determination of estrogen-related receptor gamma in the presence of phenol derivative compounds.
J.Steroid Biochem.Mol.Biol., 108:44-54, 2008

PubMed Abstract: We screened the ligand-binding domain of estrogen-related receptor (ERR) gamma in ThermoFluor, in an effort to develop chemical tools and decipher the biology of this orphan nuclear receptor. Several ligands were found to stabilize thermodynamically the protein. Amongst the ligands were bisphenol A (BPA) and 4-chloro-3-methyl phenol (ClCH3Ph). These ligands were further characterized and found to be competitive for 4-hydroxytamoxifen (4OHT) binding, a known reported antagonist ligand for ERRgamma, but functionally they did not enhance or disrupt affinity of the receptor for co-activator peptides. The preservation of the constitutive active conformation of the receptor in the presence of these two ligands was confirmed upon the determination of the co-crystal structures. The structures of BPA and ClCH3Ph were determined to a resolution of 2.1 and 2.3A, respectively, and the antagonist 4OHT was refined to 2.5A resolution. In the presence of BPA and ClCH3Ph the receptor maintained the transcriptional active conformation as reported previously for the apo-protein in the presence of a co-activator peptide fragment. In addition the ERRgamma-BPA structure identifies an interaction between the phenolic-OH and the side chain of N346. The preservation of the constitutive active conformation of the receptor in the presence of the small phenol compounds suggest that the biological activity of the receptor might be regulated by a natural occurring ligand.

PubMed: 17964775
DOI: 10.1016/j.jsbmb.2007.06.006

実験手法

X-RAY DIFFRACTION (2.3 Å)