O2 activation in salicylate 1,2-dioxygenase : A QM/MM study reveals the role of His162
(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.
(Less)
- author
- Dong, Geng LU and Ryde, Ulf LU
- organization
- publishing date
- 2016-11-21
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Inorganic Chemistry
- volume
- 55
- issue
- 22
- pages
- 9 pages
- publisher
- The American Chemical Society (ACS)
- external identifiers
-
- scopus:84998655177
- pmid:27801577
- 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
- 2024-03-22 14:18:59
@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 (ACS)}}, series = {{Inorganic Chemistry}}, title = {{O<sub>2</sub> activation in salicylate 1,2-dioxygenase : A QM/MM study reveals the role of His162}}, url = {{https://lup.lub.lu.se/search/files/20966876/sdo_with_correction.pdf}}, doi = {{10.1021/acs.inorgchem.6b01732}}, volume = {{55}}, year = {{2016}}, }