5ICF

Crystal structure of (S)-norcoclaurine 6-O-methyltransferase with S-adenosyl-L-homocysteine and sanguinarine

5ICF の概要

• エントリーDOI: 10.2210/pdb5icf/pdb
• 分子名称: (S)-norcoclaurine 6-O-methyltransferase, S-ADENOSYL-L-HOMOCYSTEINE, 13-methyl[1,3]benzodioxolo[5,6-c][1,3]dioxolo[4,5-i]phenanthridin-13-ium, ... (8 entities in total)
• 機能のキーワード: methyltransferase, benzylisoquinoline alkaloid, transferase
• 由来する生物種: Thalictrum flavum subsp. glaucum (Yellow meadow rue)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 41312.74

構造登録者

Robin, A.Y.,Graindorge, M.,Giustini, C.,Dumas, R.,Matringe, M. (登録日: 2016-02-23, 公開日: 2016-06-08, 最終更新日: 2024-05-08)

主引用文献

Robin, A.Y.,Giustini, C.,Graindorge, M.,Matringe, M.,Dumas, R.
Crystal structure of norcoclaurine-6-O-methyltransferase, a key rate-limiting step in the synthesis of benzylisoquinoline alkaloids.
Plant J., 87:641-653, 2016

PubMed Abstract: Growing pharmaceutical interest in benzylisoquinoline alkaloids (BIA) coupled with their chemical complexity make metabolic engineering of microbes to create alternative platforms of production an increasingly attractive proposition. However, precise knowledge of rate-limiting enzymes and negative feedback inhibition by end-products of BIA metabolism is of paramount importance for this emerging field of synthetic biology. In this work we report the structural characterization of (S)-norcoclaurine-6-O-methyltransferase (6OMT), a key rate-limiting step enzyme involved in the synthesis of reticuline, the final intermediate to be shared between the different end-products of BIA metabolism, such as morphine, papaverine, berberine and sanguinarine. Four different crystal structures of the enzyme from Thalictrum flavum (Tf 6OMT) were solved: the apoenzyme, the complex with S-adenosyl-l-homocysteine (SAH), the complexe with SAH and the substrate and the complex with SAH and a feedback inhibitor, sanguinarine. The Tf 6OMT structural study provides a molecular understanding of its substrate specificity, active site structure and reaction mechanism. This study also clarifies the inhibition of Tf 6OMT by previously suggested feedback inhibitors. It reveals its high and time-dependent sensitivity toward sanguinarine.

PubMed: 27232113
DOI: 10.1111/tpj.13225

実験手法

X-RAY DIFFRACTION (1.8 Å)