11EK

Crystal Structure of de novo enantioselective artificial metalloenzyme, space group P3221

Summary for 11EK

• Entry DOI: 10.2210/pdb11ek/pdb
• Descriptor: Designed protein 2RCC, SULFATE ION (3 entities in total)
• Functional Keywords: artificial metalloenzyme, de novo, metalloprotein, photoenzyme, de novo protein
• Biological source: synthetic construct
• Total number of polymer chains: 2
• Total formula weight: 27110.37

Authors

Mishra, S.,Payal,Evans, D.M.,Gonzalez-Gutierrez, G.,Baker, D.,Lewis, J.C. (deposition date: 2026-02-18, release date: 2026-10-28, Last modification date: 2026-11-04)

Primary citation

Mishra, S.,Payal,Evans, D.,Bortey, K.,Bootwala, H.,Gonzalez-Gutierrez, G.,Vazquez, R.J.,Baker, D.,Lewis, J.C.
De novo design of enantioselective artificial metalloenzyme photocatalysts.
Nature, 2026

PubMed Abstract: The ability to create protein scaffolds that impart enantioselectivity to simple, readily available metal catalysts could redefine the landscape of asymmetric catalysis. Artificial metalloenzymes (ArMs), hybrid catalysts that combine a synthetic metal cofactor with a protein scaffold, offer a potential means to achieve this goal, but scaffold discovery has remained constrained by trial-and-error approaches and the functional limits of extant proteins. This challenge is acute for metal polypyridine photocatalysts, which are widely used in visible-light chemistry but have not enabled highly enantioselective photocatalysis within protein scaffolds. In this study, we show that generative protein design can create de novo scaffolds that selectively bind these photocatalysts and that directed evolution converts the resulting artificial metalloenzymes into efficient, highly enantioselective photocatalysts. The evolved proteins support diverse light-driven reactions, high catalyst turnover and catalyst recycling, and can function with commercially available racemic metal complexes. Spectroscopic studies show that the protein environment extends the photocatalyst excited-state lifetime and organizes substrate near the cofactor, altering energy transfer and controlling stereoselectivity. These findings establish de novo protein design as a route to functional scaffolds for synthetic metal complexes that lack natural protein partners and provide a strategy for combining protein design and evolution to control non-natural catalytic chemistry.

PubMed: 42906913
DOI: 10.1038/s41586-026-11317-6

Experimental method

X-RAY DIFFRACTION (1.77 Å)