7TWL

Structure of a borosin methyltransferase from Mycena rosella with peptide A2 (MroMA2) in complex with SAH

7TWL の概要

• エントリーDOI: 10.2210/pdb7twl/pdb
• 分子名称: MroMA2, S-ADENOSYL-L-HOMOCYSTEINE (3 entities in total)
• 機能のキーワード: ripps, methyltransferase, borosin, mroma, transferase
• 由来する生物種: Mycena rosella
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 177014.10

構造登録者

Zheng, Y.,Ongpipattanakul, C.,Nair, S.K. (登録日: 2022-02-07, 公開日: 2022-11-02, 最終更新日: 2024-10-09)

主引用文献

Zheng, Y.,Ongpipattanakul, C.,Nair, S.K.
Bioconjugate Platform for Iterative Backbone N -Methylation of Peptides.
Acs Catalysis, 12:14006-14014, 2022

PubMed Abstract: -methylation of peptide backbones has often been utilized as a strategy towards the development of peptidic drugs. However, difficulties in the chemical synthesis, high cost of enantiopure -methyl building blocks, and subsequent coupling inefficiencies have hampered larger-scale medicinal chemical efforts. Here, we present a chemoenzymatic strategy for backbone -methylation by bioconjugation of peptides of interest to the catalytic scaffold of a borosin-type methyltransferase. Crystal structures of a substrate tolerant enzyme from guided the design of a decoupled catalytic scaffold that can be linked via a heterobifunctional crosslinker to any peptide substrate of choice. Peptides linked to the scaffold, including those with non-proteinogenic residues, show robust backbone -methylation. Various crosslinking strategies were tested to facilitate substrate disassembly, which enabled a reversible bioconjugation approach that efficiently released modified peptide. Our results provide general framework for the backbone -methylation on any peptide of interest and may facilitate the production of large libraries of -methylated peptides.

PubMed: 36793448
DOI: 10.1021/acscatal.2c04681

実験手法

X-RAY DIFFRACTION (1.86 Å)