9OER

HalA with lysine, Fe(II), chloride, and a peroxyhemiketal intermediate

This is a non-PDB format compatible entry.

Summary for 9OER

• Entry DOI: 10.2210/pdb9oer/pdb
• Descriptor: Lysine halogenase, LYSINE, 2-OXOGLUTARIC ACID, ... (9 entities in total)
• Functional Keywords: halogenase, fe/2og oxidase, biosynthetic protein
• Biological source: Actinoplanes teichomyceticus
• Total number of polymer chains: 8
• Total formula weight: 241594.29

Authors

Kissman, E.N.,Yang, A.Y.,Chang, M.C.Y. (deposition date: 2025-04-29, release date: 2025-11-19, Last modification date: 2025-12-03)

Primary citation

Kissman, E.N.,Kipouros, I.,Slater, J.W.,Stone, E.A.,Yang, A.Y.,Braun, A.,Ensberg, A.R.,Whitten, A.M.,Chatterjee, K.,Bogacz, I.,Yano, J.,Martin Bollinger Jr., J.,Chang, M.C.Y.
Dynamic metal coordination controls chemoselectivity in a radical halogenase.
Nat.Chem.Biol., 2025

PubMed Abstract: The activation of inert C(sp)-H bonds by nonheme Fe enzymes provides a powerful biocatalytic platform for the chemical synthesis of molecules with increased sp complexity. In this context, Fe/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 activation pathway of Fe/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.

PubMed: 41272319
DOI: 10.1038/s41589-025-02077-x

Experimental method

X-RAY DIFFRACTION (1.72 Å)