9DTH

Tyr-His linked F33Y CuBMb

9DTH の概要

• エントリーDOI: 10.2210/pdb9dth/pdb
• 関連するPDBエントリー: 4FWX
• 分子名称: Myoglobin, PROTOPORPHYRIN IX CONTAINING FE, OXYGEN ATOM, ... (4 entities in total)
• 機能のキーワード: oxidase, metalloenzyme, oxidoreductase
• 由来する生物種: Physeter catodon (sperm whale)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 18030.60

構造登録者

Lu, Y.,Liu, Y. (登録日: 2024-10-01, 公開日: 2025-10-15, 最終更新日: 2025-10-29)

主引用文献

Liu, Y.,Vilbert, A.C.,Ghosh, B.,Young, R.P.,Merkley, E.D.,Mukherjee, A.,Phan, L.,Van Stappen, C.,Baghi-Damodaran, A.,Miner, K.D.,Adkins, J.,Cort, J.,Lu, Y.
A Post-translational Histidine-Histidine Cross-Link Enhances Enzymatic Oxygen Reduction Activity with Greater pH Adaptability.
J.Am.Chem.Soc., 147:37688-37700, 2025

PubMed Abstract: Cross-linked protein residues exist as enzyme cofactors to enable or enhance catalytic activities. Despite their importance in nature, the chemical identity of the cross-links is limited to certain amino acid combinations, whose function and the formation mechanism remain insufficiently understood due to the difficulty in isolating native enzymes without the cross-links. Herein, we report the formation and characterization of both His-Tyr and His-His cross-links under oxidative enzymatic turnover conditions in L29H/F33Y/F43H Mb, a structural and functional model of heme-copper oxidase (HCO). The connectivity of the cross-link was characterized as N(His29)-C(His43) by mass spectrometry (LC-MS/MS) and nuclear magnetic resonance (NMR). Interestingly, formation of the cross-link significantly enhances the oxygen reduction activity of the enzyme at neutral or basic pH with higher product specificity. X-ray crystallography has identified a novel Tyr-His cross-link through a Tyr-O-His linkage. Our mechanistic studies indicate the involvement of high-valent heme-iron and the neighboring tyrosine in an oxidative self-processing pathway to generate the cross-link. This work serves as a new example while providing insights into the enzyme cross-link formation, allowing the design of artificial biocatalysts containing these novel cross-links with higher activity and pH adaptability.

PubMed: 41047894
DOI: 10.1021/jacs.5c12710

実験手法

X-RAY DIFFRACTION (1.8 Å)