9OET | pdb_00009oet

Dynamic metal coordination controls chemoselectivity in a radical halogenase.

(2025) Nat Chem Biol 

• PubMed: 41272319 Search on PubMedSearch on PubMed Central
• DOI: https://doi.org/10.1038/s41589-025-02077-x
• Primary Citation of Related Structures:  
  9OER, 9OES, 9OET, 9OEU, 9OEV, 9OEW


• PubMed Abstract: 
  

  The activation of inert C(sp ³ )-H bonds by nonheme Fe enzymes provides a powerful biocatalytic platform for the chemical synthesis of molecules with increased sp ³ complexity. In this context, Fe ^II /α-ketoglutarate-dependent radical halogenases are uniquely capable of carrying out transfer of a diverse array of bound anions following C-H activation. Here, we provide experimental evidence that bifurcation of radical rebound after H-atom abstraction can be driven both by the ability of a dynamic metal coordination sphere to reorganize and by a second-sphere hydrogen-bonding network where only two residues are sufficient. In addition, we present crystallographic data supporting the existence of an early peroxyhemiketal intermediate in the O ₂ activation pathway of Fe ^II /α-ketoglutarate-dependent enzymes. These data provide a paradigm for understanding the evolution of catalytic plasticity in these enzymes and yields insight into the design principles by which to expand their reaction scope.

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Organizational Affiliation: 
• Department of Chemistry, University of California, Berkeley, CA, USA.
Miller Institute for Basic Research in Science, University of California, Berkeley, CA, USA.
Department of Chemistry, The Pennsylvania State University, University Park, PA, USA.
Department of Chemistry and Biochemistry, Fairfield University, Fairfield, CT, USA.
Department of Chemistry, Stanford University, Stanford, CA, USA.
Department of Chemical & Biomolecular Engineering, University of California, Berkeley, CA, USA.
Molecular Biophysics and Integrated Bioimaging Division, Lawrence Berkeley National Laboratory, Berkeley, CA, USA.
Department of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, PA, USA.
Department of Chemistry, University of California, Berkeley, CA, USA. mcchang@princeton.edu.
Department of Chemical & Biomolecular Engineering, University of California, Berkeley, CA, USA. mcchang@princeton.edu.
Department of Chemistry, Princeton University, Princeton, NJ, USA. mcchang@princeton.edu.
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