9T8B

Crystal structure de novo CO2 reductase A4H73A

Summary for 9T8B

• Entry DOI: 10.2210/pdb9t8b/pdb
• Descriptor: de novo CO2 reductase, DI(HYDROXYETHYL)ETHER, TETRAETHYLENE GLYCOL, ... (6 entities in total)
• Functional Keywords: de novo co2 reductase, oxidoreductase
• Biological source: synthetic construct
• Total number of polymer chains: 2
• Total formula weight: 39024.83

Authors

Levy, C.W.,Ortmayer, M. (deposition date: 2025-11-12, release date: 2026-07-29)

Primary citation

Radley, E.J.,Andrews, A.C.,Kalvet, I.,Deng, Y.,Bell, E.L.,Levy, C.W.,Ortmayer, M.,Heyes, D.J.,Megarity, C.F.,Nunez-Franco, R.,Hutton, A.E.,Lu, Y.,Baker, D.,Green, A.P.
A De Novo CO 2 Reductase Featuring a Cysteine-Ligated Cobalt Porphyrin Cofactor.
J.Am.Chem.Soc., 2026

PubMed Abstract: Modern protein design methods based on deep learning allow generation of customized protein scaffolds with diverse geometries and functionalities. Here we capitalize on these recent advances to develop hyper-thermostable CO reductases featuring a cobalt porphyrin IX (CoPPIX) cofactor. CoPPIX-containing enzymes were assembled through media supplementation with cobalt salts and assessed for photocatalytic CO reductase activity. We identified two cysteine-ligated designs that exhibit high activity (>1000 turnovers at rates of up to 25 min) while suppressing competing hydrogen evolution pathways. A 2.1 Å crystal structure shows close agreement to the design model with the Co-Cys bond programmed as intended. This study showcases the power of computational protein design in developing artificial enzymes to activate challenging molecules such as CO.

PubMed: 42425911
DOI: 10.1021/jacs.6c07615

Experimental method

X-RAY DIFFRACTION (1.81 Å)