9CHK

Structure of the alpha-N-methyltransferase (SonM) and RiPP precursor (SonA-Y62A) heteromeric complex (bound to SAM)

9CHK の概要

• エントリーDOI: 10.2210/pdb9chk/pdb
• 関連するPDBエントリー: 7LTE 7LTF 7LTH 7LTR 7LTS 8T1S 8T1T 9CGW 9CH0 9CH1 9CH2 9CH3 9CH5 9CH7 9CHI
• 分子名称: TP-methylase family protein, Extradiol ring-cleavage dioxygenase LigAB LigA subunit domain-containing protein, S-ADENOSYLMETHIONINE, ... (5 entities in total)
• 機能のキーワード: alpha-n-methyltransferase, transferase
• 由来する生物種: Shewanella oneidensis; 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 76498.88

構造登録者

Crone, K.K.,Labonte, J.W.,Elias, M.,Freeman, M.F. (登録日: 2024-07-01, 公開日: 2025-01-29)

主引用文献

Crone, K.K.,Labonte, J.W.,Elias, M.H.,Freeman, M.F.
alpha-N-Methyltransferase regiospecificity is mediated by proximal, redundant enzyme-substrate interactions.
Protein Sci., 34:e70021-e70021, 2025

PubMed Abstract: N-Methylation of the peptide backbone confers pharmacologically beneficial characteristics to peptides that include greater membrane permeability and resistance to proteolytic degradation. The borosin family of ribosomally synthesized and post-translationally modified peptides offer a post-translational route to install amide backbone α-N-methylations. Previous work has elucidated the substrate scope and engineering potential of two examples of type I borosins, which feature autocatalytic precursors that encode N-methyltransferases that methylate their own C-termini in trans. We recently reported the first discrete N-methyltransferase and precursor peptide from Shewanella oneidensis MR-1, a minimally iterative, type IV borosin that allowed the first detailed kinetic analyses of borosin N-methyltransferases. Herein, we characterize the substrate scope and resilient regiospecificity of this discrete N-methyltransferase by comparison of relative rates and methylation patterns of over 40 precursor peptide variants along with structure analyses of nine enzyme-substrate complexes. Sequences critical to methylation are identified and demonstrated in assaying minimal peptide substrates and non-native peptide sequences for assessment of secondary structure requirements and engineering potential. This work grants understanding towards the mechanism of substrate recognition and iterative activity by discrete borosin N-methyltransferases.

PubMed: 39840790
DOI: 10.1002/pro.70021

実験手法

X-RAY DIFFRACTION (1.5 Å)