O2 activation in salicylate 1,2-dioxygenase : A QM/MM study reveals the role of His162

• Nonheme iron enzymes play an important role in the aerobic degradation of aromatic ring systems. Most enzymes can only cleave substrates with electron-rich substituents, e.g., with two hydroxyl groups. However, salicylate 1,2-dioxygenase (SDO) can cleave rings with only a single hydroxyl group. We investigated the oxygen-activation mechanism of the ring fission of salicylate by SDO by computational methods using combined quantum mechanical and molecular mechanical (QM/MM) geometry optimizations, large QM calculations with 493 atoms, and QM/MM free-energy perturbations. Our results demonstrate that the reactive Fe-O2 species is best described as a Fe(III)-O2•- state, which is triplet O2 binding to quintet Fe(II), leading to a one-electron transfer from Fe(II) to O2. Subsequently, the O2•- group of this species attacks the aromatic ring of substrate to form an alkylperoxo intermediate. Mutation studies suggested that His162 is essential for catalysis. Our calculations indicate that His162 plays a role as an acid-base catalyst, providing a proton to the substrate.

Ämnesord

NATURVETENSKAP  -- Kemi -- Oorganisk kemi (hsv//swe)

NATURAL SCIENCES  -- Chemical Sciences -- Inorganic Chemistry (hsv//eng)

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