5N0U

Crystal structure of OphA-DeltaC6 mutant R72A in complex with SAH

5N0U の概要

• エントリーDOI: 10.2210/pdb5n0u/pdb
• 分子名称: Peptide N-Methyltransferase, S-ADENOSYL-L-HOMOCYSTEINE, MAGNESIUM ION, ... (4 entities in total)
• 機能のキーワード: methyltransferase, transferase
• 由来する生物種: Omphalotus olearius
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 45395.65

構造登録者

Song, H.,Naismith, J.H. (登録日: 2017-02-03, 公開日: 2018-02-14, 最終更新日: 2024-05-08)

主引用文献

Song, H.,van der Velden, N.S.,Shiran, S.L.,Bleiziffer, P.,Zach, C.,Sieber, R.,Imani, A.S.,Krausbeck, F.,Aebi, M.,Freeman, M.F.,Riniker, S.,Kunzler, M.,Naismith, J.H.
A molecular mechanism for the enzymatic methylation of nitrogen atoms within peptide bonds.
Sci Adv, 4:eaat2720-eaat2720, 2018

PubMed Abstract: The peptide bond, the defining feature of proteins, governs peptide chemistry by abolishing nucleophilicity of the nitrogen. This and the planarity of the peptide bond arise from the delocalization of the lone pair of electrons on the nitrogen atom into the adjacent carbonyl. While chemical methylation of an amide bond uses a strong base to generate the imidate, OphA, the precursor protein of the fungal peptide macrocycle omphalotin A, self-hypermethylates amides at pH 7 using -adenosyl methionine (SAM) as cofactor. The structure of OphA reveals a complex catenane-like arrangement in which the peptide substrate is clamped with its amide nitrogen aligned for nucleophilic attack on the methyl group of SAM. Biochemical data and computational modeling suggest a base-catalyzed reaction with the protein stabilizing the reaction intermediate. Backbone N-methylation of peptides enhances their protease resistance and membrane permeability, a property that holds promise for applications to medicinal chemistry.

PubMed: 30151425
DOI: 10.1126/sciadv.aat2720

実験手法

X-RAY DIFFRACTION (1.68 Å)