1K7L

The 2.5 Angstrom resolution crystal structure of the human PPARalpha ligand binding domain bound with GW409544 and a co-activator peptide.

1K7L の概要

• エントリーDOI: 10.2210/pdb1k7l/pdb
• 関連するPDBエントリー: 1fm6 1fm9 1k74
• 分子名称: Peroxisome proliferator activated receptor alpha, steroid receptor coactivator, 2-(1-METHYL-3-OXO-3-PHENYL-PROPYLAMINO)-3-{4-[2-(5-METHYL-2-PHENYL-OXAZOL-4-YL)-ETHOXY]-PHENYL}-PROPIONIC ACID, ... (5 entities in total)
• 機能のキーワード: the 2.5 angstrom resolution crystal structure of the human pparalpha ligand binding domain bound with gw409544 and a coactivator peptide, transcription
• 由来する生物種: Homo sapiens (human); 詳細
• 細胞内の位置: Nucleus: Q07869
• タンパク質・核酸の鎖数: 8
• 化学式量合計: 142871.19

構造登録者

Xu, H.E.,Lambert, M.H.,Montana, V.G.,Moore, L.B.,Collins, J.L.,Oplinger, J.A.,Kliewer, S.A.,Gampe Jr., R.T.,McKee, D.D.,Moore, J.T.,Willson, T.M. (登録日: 2001-10-19, 公開日: 2001-12-05, 最終更新日: 2024-02-07)

主引用文献

Xu, H.E.,Lambert, M.H.,Montana, V.G.,Plunket, K.D.,Moore, L.B.,Collins, J.L.,Oplinger, J.A.,Kliewer, S.A.,Gampe Jr., R.T.,McKee, D.D.,Moore, J.T.,Willson, T.M.
Structural determinants of ligand binding selectivity between the peroxisome proliferator-activated receptors.
Proc.Natl.Acad.Sci.USA, 98:13919-13924, 2001

PubMed Abstract: The peroxisome proliferator-activated receptors (PPARs) are transcriptional regulators of glucose, lipid, and cholesterol metabolism. We report the x-ray crystal structure of the ligand binding domain of PPAR alpha (NR1C1) as a complex with the agonist ligand GW409544 and a coactivator motif from the steroid receptor coactivator 1. Through comparison of the crystal structures of the ligand binding domains of the three human PPARs, we have identified molecular determinants of subtype selectivity. A single amino acid, which is tyrosine in PPAR alpha and histidine in PPAR gamma, imparts subtype selectivity for both thiazolidinedione and nonthiazolidinedione ligands. The availability of high-resolution cocrystal structures of the three PPAR subtypes will aid the design of drugs for the treatments of metabolic and cardiovascular diseases.

PubMed: 11698662
DOI: 10.1073/pnas.241410198

実験手法

X-RAY DIFFRACTION (2.5 Å)