6L88

Crystal structure of mineralocorticoid receptor ligand binding domain in complex with esaxerenone

6L88 の概要

• エントリーDOI: 10.2210/pdb6l88/pdb
• 分子名称: Mineralocorticoid receptor, 1-(2-hydroxyethyl)-4-methyl-N-(4-methylsulfonylphenyl)-5-[2-(trifluoromethyl)phenyl]pyrrole-3-carboxamide (2 entities in total)
• 機能のキーワード: nuclear receptor, hypertension, nuclear protein, transcription
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 118504.61

構造登録者

Takahashi, M.,Hanzawa, H. (登録日: 2019-11-05, 公開日: 2020-02-12, 最終更新日: 2023-11-22)

主引用文献

Takahashi, M.,Ubukata, O.,Homma, T.,Asoh, Y.,Honzumi, M.,Hayashi, N.,Saito, K.,Tsuruoka, H.,Aoki, K.,Hanzawa, H.
Crystal structure of the mineralocorticoid receptor ligand-binding domain in complex with a potent and selective nonsteroidal blocker, esaxerenone (CS-3150).
Febs Lett., 594:1615-1623, 2020

PubMed Abstract: Activation of the mineralocorticoid receptor (MR) has long been considered a risk factor for cardiovascular diseases. It has been reported that the novel MR blocker esaxerenone shows high potency and selectivity for MR in vitro as well as great antihypertensive and renoprotective effects in salt-sensitive hypertensive rats. Here, we determined the cocrystal structure of the MR ligand-binding domain (MR-LBD) with esaxerenone and found that esaxerenone binds to MR-LBD in a unique manner with large side-chain rearrangements, distinct from those of previously published MR antagonists. This structure also displays an antagonist form that has not been observed for MR previously. Such a unique binding mode of esaxerenone provides great insight into the novelty, potency, and selectivity of this novel antihypertensive drug.

PubMed: 31991486
DOI: 10.1002/1873-3468.13746

実験手法

X-RAY DIFFRACTION (3 Å)