7P83

Crystal structure of Apo form of S-adenosylmethionine synthetase from Methanocaldococcus jannaschii

7P83 の概要

• エントリーDOI: 10.2210/pdb7p83/pdb
• 分子名称: S-adenosylmethionine synthase (2 entities in total)
• 機能のキーワード: transferase
• 由来する生物種: Methanocaldococcus jannaschii (strain ATCC 43067 / DSM 2661 / JAL-1 / JCM 10045 / NBRC 100440) (Methanococcus jannaschii)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 94970.98

構造登録者

Herrmann, E.,Peters, A.,Cornelissen, N.V.,Rentmeister, A.,Kuemmel, D. (登録日: 2021-07-21, 公開日: 2021-11-17, 最終更新日: 2024-01-31)

主引用文献

Peters, A.,Herrmann, E.,Cornelissen, N.V.,Klocker, N.,Kummel, D.,Rentmeister, A.
Visible-Light Removable Photocaging Groups Accepted by MjMAT Variant: Structural Basis and Compatibility with DNA and RNA Methyltransferases.
Chembiochem, 23:e202100437-e202100437, 2022

PubMed Abstract: Methylation and demethylation of DNA, RNA and proteins constitutes a major regulatory mechanism in epigenetic processes. Investigations would benefit from the ability to install photo-cleavable groups at methyltransferase target sites that block interactions with reader proteins until removed by non-damaging light in the visible spectrum. Engineered methionine adenosyltransferases (MATs) have been exploited in cascade reactions with methyltransferases (MTases) to modify biomolecules with non-natural groups, including first evidence for accepting photo-cleavable groups. We show that an engineered MAT from Methanocaldococcus jannaschii (PC-MjMAT) is 308-fold more efficient at converting ortho-nitrobenzyl-(ONB)-homocysteine than the wildtype enzyme. PC-MjMAT is active over a broad range of temperatures and compatible with MTases from mesophilic organisms. We solved the crystal structures of wildtype and PC-MjMAT in complex with AdoONB and a red-shifted derivative thereof. These structures reveal that aromatic stacking interactions within the ligands are key to accommodating the photocaging groups in PC-MjMAT. The enlargement of the binding pocket eliminates steric clashes to enable AdoMet analogue binding. Importantly, PC-MjMAT exhibits remarkable activity on methionine analogues with red-shifted ONB-derivatives enabling photo-deprotection of modified DNA by visible light.

PubMed: 34606675
DOI: 10.1002/cbic.202100437

実験手法

X-RAY DIFFRACTION (2.218 Å)