9EQF

Crystal structure of the L-arginine hydroxylase VioC MeHis316, bound to Fe(II), L-arginine, and succinate

Summary for 9EQF

• Entry DOI: 10.2210/pdb9eqf/pdb
• Descriptor: Alpha-ketoglutarate-dependent L-arginine hydroxylase, FE (II) ION, SUCCINIC ACID, ... (7 entities in total)
• Functional Keywords: non canonical amino acid, hydroxylate, 2og oxygenase, oxidoreductase
• Biological source: synthetic construct
• Total number of polymer chains: 1
• Total formula weight: 43840.77

Authors

Hardy, F.J. (deposition date: 2024-03-21, release date: 2024-07-31, Last modification date: 2024-08-21)

Primary citation

Hardy, F.J.,Quesne, M.G.,Gerard, E.F.,Zhao, J.,Ortmayer, M.,Taylor, C.J.,Ali, H.S.,Slater, J.W.,Levy, C.W.,Heyes, D.J.,Bollinger Jr., J.M.,de Visser, S.P.,Green, A.P.
Probing Ferryl Reactivity in a Nonheme Iron Oxygenase Using an Expanded Genetic Code.
Acs Catalysis, 14:11584-11590, 2024

PubMed Abstract: The ability to introduce noncanonical amino acids as axial ligands in heme enzymes has provided a powerful experimental tool for studying the structure and reactivity of their Fe=O ("ferryl") intermediates. Here, we show that a similar approach can be used to perturb the conserved Fe coordination environment of 2-oxoglutarate (2OG) dependent oxygenases, a versatile class of enzymes that employ highly-reactive ferryl intermediates to mediate challenging C-H functionalizations. Replacement of one of the cis-disposed histidine ligands in the oxygenase VioC with a less electron donating -methyl-histidine (MeHis) preserves both catalytic function and reaction selectivity. Significantly, the key ferryl intermediate responsible for C-H activation can be accumulated in both the wildtype and the modified protein. In contrast to heme enzymes, where metal-oxo reactivity is extremely sensitive to the nature of the proximal ligand, the rates of C-H activation and the observed large kinetic isotope effects are only minimally affected by axial ligand replacement in VioC. This study showcases a powerful tool for modulating the coordination sphere of nonheme iron enzymes that will enhance our understanding of the factors governing their divergent activities.

PubMed: 39114090
DOI: 10.1021/acscatal.4c02365

Experimental method

X-RAY DIFFRACTION (1.6 Å)