10YM

Crystal structure of a computationally designed protein bound to a Mn-containing cofactor (L1-dnMSBP)

This is a non-PDB format compatible entry.

Summary for 10YM

• Entry DOI: 10.2210/pdb10ym/pdb
• Descriptor: L1-dnMSBP, chlorido[2,2'-{(1R,2R)-cyclohexane-1,2-diylbis[(azanylylidene-kappaN)methanylylidene]}bis(4,6-di-tert-butylphenolato-kappaO)]manganate (3 entities in total)
• Functional Keywords: artificial metalloenzyme, de novo protein
• Biological source: synthetic construct
• Total number of polymer chains: 1
• Total formula weight: 24964.50

Authors

Wang, J.-X.,Lu, Y. (deposition date: 2026-02-12, release date: 2026-09-30)

Primary citation

Wang, J.X.,Deng, Y.,Kalvet, I.,Haque, A.,Dai, H.,Baker, D.,Lu, Y.
De Novo Design and Structural Optimization of Mn(salen)-Based Artificial Metalloenzymes for Asymmetric Sulfoxidation.
Angew.Chem.Int.Ed.Engl., :e5852828-e5852828, 2026

PubMed Abstract: Artificial metalloenzymes (ArMs) exhibit exceptional selectivity, yet extending their reactivity beyond native cofactors remains a major challenge. While previous designs using native protein scaffolds to incorporate nonnative cofactors have been reported, de novo protein design enables tailored scaffolds that incorporate nonnative cofactors, unlocking transformations inaccessible to natural enzymes. Here, we report the computational design of de novo proteins that bind Mn(salen)-based complexes for asymmetric sulfoxidation. The resulting ArMs outperform the free cofactor, achieving up to 45% yield and an enantiomeric ratio (e.r.) of 26:74 under optimized conditions. A 1.5 Å resolution crystal structure confirms the designed architecture and reveals key secondary-sphere interactions that govern reactivity. Guided by these insights, rational mutagenesis enhanced performance up to 79% yield and an e.r. up to 16:84. This work establishes a general strategy for integrating complex nonnative cofactors into de novo scaffolds, enabling selective catalysts for reactions beyond the reach of natural enzymes.

PubMed: 42758048
DOI: 10.1002/anie.5852828

Experimental method

X-RAY DIFFRACTION (1.5 Å)