6GY1

rat COMT in complex with inhibitor

6GY1 の概要

• エントリーDOI: 10.2210/pdb6gy1/pdb
• 分子名称: Catechol O-methyltransferase, MAGNESIUM ION, S-ADENOSYL-L-HOMOCYSTEINE, ... (6 entities in total)
• 機能のキーワード: magnesium ion binding, o-methyltransferase activity, neurotransmitter catabolic process, transferase
• 由来する生物種: Rattus norvegicus (Rat)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 25720.72

構造登録者

Schulze, M.-S. (登録日: 2018-06-27, 公開日: 2018-10-10, 最終更新日: 2025-12-10)

主引用文献

Buchler, I.,Akuma, D.,Au, V.,Carr, G.,de Leon, P.,DePasquale, M.,Ernst, G.,Huang, Y.,Kimos, M.,Kolobova, A.,Poslusney, M.,Wei, H.,Swinnen, D.,Montel, F.,Moureau, F.,Jigorel, E.,Schulze, M.E.D.,Wood, M.,Barrow, J.C.
Optimization of 8-Hydroxyquinolines as Inhibitors of Catechol O-Methyltransferase.
J. Med. Chem., 61:9647-9665, 2018

PubMed Abstract: A series of 8-hydroxy quinolines were identified as potent inhibitors of catechol O-methyltransferase (COMT) with selectivity for the membrane-bound form of the enzyme. Small substituents at the 7-position of the quinoline were found to increase metabolic stability without sacrificing potency. Compounds with good pharmacokinetics and brain penetration were identified and demonstrated in vivo modulation of dopamine metabolites in the brain. An X-ray cocrystal structure of compound 21 in the S-COMT active site shows chelation of the active site magnesium similar to catechol-based inhibitors. These compounds should prove useful for treatment of many neurological and psychiatric conditions associated with compromised cortical dopamine signaling.

PubMed: 30272964
DOI: 10.1021/acs.jmedchem.8b01126

実験手法

X-RAY DIFFRACTION (2.1 Å)