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

Dong, Geng LU and Ryde, Ulf LU (2016) In Inorganic Chemistry 55(22). p.11727-11735
Abstract

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... (More)

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.

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Inorganic Chemistry
volume
55
issue
22
pages
9 pages
publisher
The American Chemical Society
external identifiers
  • scopus:84998655177
  • wos:000388548300016
ISSN
0020-1669
DOI
10.1021/acs.inorgchem.6b01732
language
English
LU publication?
yes
id
d1c1338b-ba62-484e-a275-3aeec0a15840
date added to LUP
2016-12-19 09:54:34
date last changed
2017-11-03 00:01:00
@article{d1c1338b-ba62-484e-a275-3aeec0a15840,
  abstract     = {<p>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-O<sub>2</sub> species is best described as a Fe(III)-O<sub>2</sub>•- state, which is triplet O<sub>2</sub> binding to quintet Fe(II), leading to a one-electron transfer from Fe(II) to O<sub>2</sub>. Subsequently, the O<sub>2</sub>•- 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.</p>},
  author       = {Dong, Geng and Ryde, Ulf},
  issn         = {0020-1669},
  language     = {eng},
  month        = {11},
  number       = {22},
  pages        = {11727--11735},
  publisher    = {The American Chemical Society},
  series       = {Inorganic Chemistry},
  title        = {O<sub>2</sub> activation in salicylate 1,2-dioxygenase : A QM/MM study reveals the role of His162},
  url          = {http://dx.doi.org/10.1021/acs.inorgchem.6b01732},
  volume       = {55},
  year         = {2016},
}