8DSJ

Peptidylglycine alpha hydroxylating monooxygenase anaerobic

8DSJ の概要

• エントリーDOI: 10.2210/pdb8dsj/pdb
• 分子名称: Peptidylglycine alpha-amidating monooxygenase, COPPER (II) ION, GLYCEROL (3 entities in total)
• 機能のキーワード: copper, monooxygenase, peptidylglycine alpha hydroxylating, oxidoreductase
• 由来する生物種: Rattus norvegicus (Norway rat)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 69997.03

構造登録者

Arias, R.J.,Blackburn, N.J. (登録日: 2022-07-22, 公開日: 2023-03-22, 最終更新日: 2024-11-13)

主引用文献

Arias, R.J.,Welch, E.F.,Blackburn, N.J.
New structures reveal flexible dynamics between the subdomains of peptidylglycine monooxygenase. Implications for an open to closed mechanism.
Protein Sci., 32:e4615-e4615, 2023

PubMed Abstract: Peptidylglycine monooxygenase (PHM) is essential for the biosynthesis of many neuroendocrine peptides via a copper-dependent hydroxylation of a glycine-extended pro-peptide. The "canonical" mechanism requires the transfer of two electrons from one mononuclear copper (CuH, H-site) to a second mononuclear copper (CuM, M-site) which is the site of oxygen binding and catalysis. In most crystal structures the copper centers are separated by 11 Å of disordered solvent, but recent work has established that a PHM variant H108A forms a closed conformer in the presence of citrate with a reduced Cu-Cu site separation of ~4 Å. Here we report three new PHM structures where the H and M sites are separated by a longer distance of ~14 Å. Variation in Cu-Cu distance is the result of a rotation of the M subdomain about a hinge point centered on the pro -leu -ile triad which forms the linker between subdomains. The energetic cost of domain dynamics is likely small enough to allow free rotation of the subdomains relative to each other, adding credence to recent suggestions that an open-to-closed transition to form a binuclear oxygen binding intermediate is an essential element of catalysis. This inference would explain many experimental observations that are inconsistent with the current canonical mechanism including substrate-induced oxygen activation and isotope scrambling during the peroxide shunt.

PubMed: 36880254
DOI: 10.1002/pro.4615

実験手法

X-RAY DIFFRACTION (2.8 Å)