7P84

Crystal structure of L147A/I351A variant of S-adenosylmethionine synthetase from Methanocaldococcus jannaschii in complex with ONB-SAM (2-nitro benzyme S-adenosyl-methionine)

Summary for 7P84

• Entry DOI: 10.2210/pdb7p84/pdb
• Descriptor: S-adenosylmethionine synthase, TRIPHOSPHATE, MAGNESIUM ION, ... (5 entities in total)
• Functional Keywords: transferase
• Biological source: Methanocaldococcus jannaschii (strain ATCC 43067 / DSM 2661 / JAL-1 / JCM 10045 / NBRC 100440) (Methanococcus jannaschii)
• Total number of polymer chains: 2
• Total formula weight: 95912.04

Authors

Herrmann, E.,Peters, A.,Cornelissen, N.V.,Rentmeister, A.,Kuemmel, D. (deposition date: 2021-07-21, release date: 2021-11-17, Last modification date: 2024-01-31)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.054 Å)