6TSC

OphMA I407P complex with SAH

6TSC の概要

• エントリーDOI: 10.2210/pdb6tsc/pdb
• 分子名称: Peptide N-methyltransferase, GLY-PHE-PRO-TRP-MVA-ILE-MVA-VAL-GLY-VAL-PRO-GLY, S-ADENOSYL-L-HOMOCYSTEINE, ... (4 entities in total)
• 機能のキーワード: peptide bond n-methyltransferase, transferase
• 由来する生物種: Omphalotus olearius; 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 47257.72

構造登録者

Song, H.,Naismith, J.H. (登録日: 2019-12-20, 公開日: 2020-06-24, 最終更新日: 2024-11-13)

主引用文献

Song, H.,Fahrig-Kamarauskaite, J.R.,Matabaro, E.,Kaspar, H.,Shirran, S.L.,Zach, C.,Pace, A.,Stefanov, B.A.,Naismith, J.H.,Kunzler, M.
Substrate Plasticity of a Fungal Peptide alpha-N-Methyltransferase.
Acs Chem.Biol., 15:1901-1912, 2020

PubMed Abstract: The methylation of amide nitrogen atoms can improve the stability, oral availability, and cell permeability of peptide therapeutics. Chemical -methylation of peptides is challenging. Omphalotin A is a ribosomally synthesized, macrocylic dodecapeptide with nine backbone -methylations. The fungal natural product is derived from the precursor protein, OphMA, harboring both the core peptide and a SAM-dependent peptide α--methyltransferase domain. OphMA forms a homodimer and its α--methyltransferase domain installs the methyl groups on the hydrophobic core dodecapeptide and some additional C-terminal residues of the protomers. These post-translational backbone -methylations occur in a processive manner from the N- to the C-terminus of the peptide substrate. We demonstrate that OphMA can methylate polar, aromatic, and charged residues when these are introduced into the core peptide. Some of these amino acids alter the efficiency and pattern of methylation. Proline, depending on its sequence context, can act as a tunable stop signal. Crystal structures of OphMA variants have allowed rationalization of these observations. Our results hint at the potential to control this fungal α--methyltransferase for biotechnological applications.

PubMed: 32491837
DOI: 10.1021/acschembio.0c00237

実験手法

X-RAY DIFFRACTION (2.19 Å)