5TDT

Oxygenated toluene intermediate in toluene 4-monooxygenase (T4moHD) after reaction in the crystal

Summary for 5TDT

• Entry DOI: 10.2210/pdb5tdt/pdb
• Related: 5TDS 5TDU 5TDV
• Descriptor: Toluene-4-monooxygenase system protein A, Toluene-4-monooxygenase system protein E, Toluene-4-monooxygenase system protein B, ... (8 entities in total)
• Functional Keywords: intermediate, diiron, oxidoreductase
• Biological source: Pseudomonas mendocina; More
• Total number of polymer chains: 8
• Total formula weight: 230436.28

Authors

Acheson, J.F.,Fox, B.G. (deposition date: 2016-09-19, release date: 2017-03-22, Last modification date: 2023-10-04)

Primary citation

Acheson, J.F.,Bailey, L.J.,Brunold, T.C.,Fox, B.G.
In-crystal reaction cycle of a toluene-bound diiron hydroxylase.
Nature, 544:191-195, 2017

PubMed Abstract: Electrophilic aromatic substitution is one of the most important and recognizable classes of organic chemical transformation. Enzymes create the strong electrophiles that are needed for these highly energetic reactions by using O, electrons, and metals or other cofactors. Although the nature of the oxidants that carry out electrophilic aromatic substitution has been deduced from many approaches, it has been difficult to determine their structures. Here we show the structure of a diiron hydroxylase intermediate formed during a reaction with toluene. Density functional theory geometry optimizations of an active site model reveal that the intermediate is an arylperoxo Fe/Fe species with delocalized aryl radical character. The structure suggests that a carboxylate ligand of the diiron centre may trigger homolytic cleavage of the O-O bond by transferring a proton from a metal-bound water. Our work provides the spatial and electronic constraints needed to propose a comprehensive mechanism for diiron enzyme arene hydroxylation that accounts for many prior experimental results.

PubMed: 28346937
DOI: 10.1038/nature21681

Experimental method

X-RAY DIFFRACTION (1.818 Å)