6LTV

Crystal Structure of I122A/I330A variant of S-adenosylmethionine synthetase from Cryptosporidium hominis in complex with ONB-SAM (2-nitro benzyme S-adenosyl-methionine)

6LTV の概要

• エントリーDOI: 10.2210/pdb6ltv/pdb
• 分子名称: S-adenosylmethionine synthase, TRIPHOSPHATE, MAGNESIUM ION, ... (5 entities in total)
• 機能のキーワード: triphosphate, s-adenosylmethionine synthetase, transferase
• 由来する生物種: Cryptosporidium hominis
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 93347.93

構造登録者

Singh, R.K.,Michailidou, F.,Rentmeister, A.,Kuemmel, D. (登録日: 2020-01-23, 公開日: 2020-10-21, 最終更新日: 2023-11-29)

主引用文献

Michailidou, F.,Klocker, N.,Cornelissen, N.V.,Singh, R.K.,Peters, A.,Ovcharenko, A.,Kummel, D.,Rentmeister, A.
Engineered SAM Synthetases for Enzymatic Generation of AdoMet Analogs with Photocaging Groups and Reversible DNA Modification in Cascade Reactions.
Angew.Chem.Int.Ed.Engl., 60:480-485, 2021

PubMed Abstract: Methylation and demethylation of DNA, RNA and proteins has emerged as a major regulatory mechanism. Studying the function of these modifications would benefit from tools for their site-specific inhibition and timed removal. S-Adenosyl-L-methionine (AdoMet) analogs in combination with methyltransferases (MTases) have proven useful to map or block and release MTase target sites, however their enzymatic generation has been limited to aliphatic groups at the sulfur atom. We engineered a SAM synthetase from Cryptosporidium hominis (PC-ChMAT) for efficient generation of AdoMet analogs with photocaging groups that are not accepted by any WT MAT reported to date. The crystal structure of PC-ChMAT at 1.87 Å revealed how the photocaged AdoMet analog is accommodated and guided engineering of a thermostable MAT from Methanocaldococcus jannaschii. PC-MATs were compatible with DNA- and RNA-MTases, enabling sequence-specific modification ("writing") of plasmid DNA and light-triggered removal ("erasing").

PubMed: 33017502
DOI: 10.1002/anie.202012623

実験手法

X-RAY DIFFRACTION (1.87 Å)