5FHQ

Crystal structure of (WT) Rat Catechol-O-Methyltransferase in complex with AdoMet and 3,5-dinitrocatechol (DNC)

5FHQ の概要

• エントリーDOI: 10.2210/pdb5fhq/pdb
• 分子名称: Catechol O-methyltransferase, S-ADENOSYLMETHIONINE, 3,5-DINITROCATECHOL, ... (5 entities in total)
• 機能のキーワード: methyltransferase regioselectivity, transferase
• 由来する生物種: Rattus norvegicus (Norway 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: 24604.38

構造登録者

Levy, C. (登録日: 2015-12-22, 公開日: 2016-02-03, 最終更新日: 2024-01-10)

主引用文献

Law, B.J.,Bennett, M.R.,Thompson, M.L.,Levy, C.,Shepherd, S.A.,Leys, D.,Micklefield, J.
Effects of Active-Site Modification and Quaternary Structure on the Regioselectivity of Catechol-O-Methyltransferase.
Angew.Chem.Int.Ed.Engl., 55:2683-2687, 2016

PubMed Abstract: Catechol-O-methyltransferase (COMT), an important therapeutic target in the treatment of Parkinson's disease, is also being developed for biocatalytic processes, including vanillin production, although lack of regioselectivity has precluded its more widespread application. By using structural and mechanistic information, regiocomplementary COMT variants were engineered that deliver either meta- or para-methylated catechols. X-ray crystallography further revealed how the active-site residues and quaternary structure govern regioselectivity. Finally, analogues of AdoMet are accepted by the regiocomplementary COMT mutants and can be used to prepare alkylated catechols, including ethyl vanillin.

PubMed: 26797714
DOI: 10.1002/anie.201508287

実験手法

X-RAY DIFFRACTION (1.63 Å)