9JIY
Macrophage migration inhibitory factor S61H/Y100H mutant complexed with three Zinc ions (Zn3-MIF(S61H/Y100H)-L)
Summary for 9JIY
| Entry DOI | 10.2210/pdb9jiy/pdb |
| Related | 9JIT |
| Descriptor | Macrophage migration inhibitory factor, ZINC ION, CARBONATE ION, ... (7 entities in total) |
| Functional Keywords | macrophage migration inhibitory factor, cytokine |
| Biological source | Homo sapiens (human) |
| Total number of polymer chains | 3 |
| Total formula weight | 38822.10 |
| Authors | Himiyama, T.,Okamoto, Y. (deposition date: 2024-09-12, release date: 2025-08-06, Last modification date: 2025-08-13) |
| Primary citation | 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 Cited by 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: 40745177DOI: 10.1038/s41467-025-61909-5 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.2 Å) |
Structure validation
Download full validation report
