9JIY

Macrophage migration inhibitory factor S61H/Y100H mutant complexed with three Zinc ions (Zn3-MIF(S61H/Y100H)-L)

9JIY の概要

• エントリーDOI: 10.2210/pdb9jiy/pdb
• 関連するPDBエントリー: 9JIT
• 分子名称: Macrophage migration inhibitory factor, ZINC ION, CARBONATE ION, ... (7 entities in total)
• 機能のキーワード: macrophage migration inhibitory factor, cytokine
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 38822.10

構造登録者

Himiyama, T.,Okamoto, Y. (登録日: 2024-09-12, 公開日: 2025-08-06, 最終更新日: 2025-08-13)

主引用文献

Ueno, A.,Takida, F.,Kita, T.,Ishii, T.,Himiyama, T.,Mabuchi, T.,Okamoto, Y.
A cytokine-based designer enzyme with an abiological multinuclear metal center exhibits intrinsic and extrinsic catalysis.
Nat Commun, 16:6781-6781, 2025

PubMed Abstract: A designer enzyme consisting of an abiological molecule incorporated into a natural protein has been developed as an exceptionally chemoselective catalyst, highlighting that the internal space of proteins is highly beneficial for enhancing catalytic performance. However, other features of proteins have received less attention in designer enzymes, for e.g., their use as ligands to construct abiological (multinuclear) metal centers and their intrinsic functions that have often been traded off for a new function. Here, grafting a synthetic trinuclear zinc complex inside a human cytokine macrophage migration inhibitory factor (MIF) scaffold using solely amino-acid side chains leads to a designer multi-metalloenzyme with extrinsic and intrinsic functions. The crystal structure of the designer tri-zinc enzyme verifies the accuracy of our design process based on geometry optimizations and quantum-chemical calculations. The extrinsic catalytic performance of this designer enzyme is of the highest class and comparable to that of previously reported designer zinc hydrolases. Importantly, an intrinsic function of MIF, i.e., its tautomerase activity, is maintained in this designer tri-zinc enzyme. Considering that cytokines are originally expressed in response to in vivo events, this cytokine-based designer metalloenzyme holds promising potential as a synthetic biological tool for the self-adaptive regulation of life phenomena.

PubMed: 40745177
DOI: 10.1038/s41467-025-61909-5

実験手法

X-RAY DIFFRACTION (1.2 Å)