2ZVJ

Crystal structures of rat Catechol-O-Methyltransferase complexed with coumarine-based inhibitor

2ZVJ の概要

• エントリーDOI: 10.2210/pdb2zvj/pdb
• 関連するPDBエントリー: 1H1D 1JR4 1VID 2CL5
• 分子名称: Catechol O-methyltransferase, MAGNESIUM ION, S-ADENOSYLMETHIONINE, ... (5 entities in total)
• 機能のキーワード: transferase, methyltransferase, neurotransmitter degradation, alternative initiation, catecholamine metabolism, cell membrane, cytoplasm, magnesium, membrane, metal-binding, phosphoprotein, s-adenosyl-l-methionine, signal-anchor, transmembrane
• 由来する生物種: Rattus norvegicus (Rat)
• 細胞内の位置: Isoform 2: Cytoplasm. Isoform 1: Cell membrane; Single-pass type II membrane protein; Extracellular side: P22734
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 25593.51

構造登録者

Tsuji, E. (登録日: 2008-11-07, 公開日: 2009-01-06, 最終更新日: 2023-11-01)

主引用文献

Tsuji, E.,Okazaki, K.,Takeda, K.
Crystal structures of rat catechol-O-methyltransferase complexed with coumarine-based inhibitor
Biochem.Biophys.Res.Commun., 378:494-497, 2009

PubMed Abstract: In human, catechol-O-methyltransferase (COMT: E.C. 2.1.1.6) is responsible for metabolism of catechol neurotransmitter and xenobiotics. The main clinical interest in COMT results from the possibility of using COMT inhibitors as adjuncts in the therapy of Parkinson's disease (PD) with l-DOPA. COMT is therefore a target for inhibitor development aiming at PD treatment and has been submitted to extensive structure-based drug design. Recently reported inhibitors have nitrocatechol structure that may inhibit oxidative phosphorylation and uncouple mitochondrial energy production. This work reports the first crystallographic study of Rat COMT complexed with non-nitrocatechol inhibitor. Analysis of the structural differences among the previously reported inhibitor complexes, coumarine-based inhibitor (4-phenyl-7, 8-dihydroxycoumarine: 4PCM) bound structure provides the explanation for inhibitor binding and can be used for future inhibitor design.

PubMed: 19056347
DOI: 10.1016/j.bbrc.2008.11.085

実験手法

X-RAY DIFFRACTION (2.3 Å)