6GKY

Crystal structure of Coclaurine N-Methyltransferase (CNMT) bound to N-methylheliamine and SAH

6GKY の概要

• エントリーDOI: 10.2210/pdb6gky/pdb
• 関連するPDBエントリー: 6GKV
• 分子名称: Coclaurine N-methyltransferase, S-ADENOSYL-L-HOMOCYSTEINE, 6,7-dimethoxy-2,4-dihydro-1~{H}-isoquinolin-3-one (3 entities in total)
• 機能のキーワード: n-methylheliamine, coclaurine n-methyltransferase, transferase
• 由来する生物種: Coptis japonica (Japanese goldthread)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 83324.88

構造登録者

Dunstan, M.S.,Levy, C.W. (登録日: 2018-05-22, 公開日: 2018-06-06, 最終更新日: 2025-12-10)

主引用文献

Bennett, M.R.,Thompson, M.L.,Shepherd, S.A.,Dunstan, M.S.,Herbert, A.J.,Smith, D.R.M.,Cronin, V.A.,Menon, B.R.K.,Levy, C.,Micklefield, J.
Structure and Biocatalytic Scope of Coclaurine N-Methyltransferase.
Angew. Chem. Int. Ed. Engl., 57:10600-10604, 2018

PubMed Abstract: Benzylisoquinoline alkaloids (BIAs) are a structurally diverse family of plant secondary metabolites, which have been exploited to develop analgesics, antibiotics, antitumor agents, and other therapeutic agents. Biosynthesis of BIAs proceeds via a common pathway from tyrosine to (S)-reticulene at which point the pathway diverges. Coclaurine N-methyltransferase (CNMT) is a key enzyme in the pathway to (S)-reticulene, installing the N-methyl substituent that is essential for the bioactivity of many BIAs. In this paper, we describe the first crystal structure of CNMT which, along with mutagenesis studies, defines the enzymes active site architecture. The specificity of CNMT was also explored with a range of natural and synthetic substrates as well as co-factor analogues. Knowledge from this study could be used to generate improved CNMT variants required to produce BIAs or synthetic derivatives.

PubMed: 29791083
DOI: 10.1002/anie.201805060

実験手法

X-RAY DIFFRACTION (2.847 Å)