| 1. |
- Caldararu, Octav, et al.
(författare)
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QM/MM study of the reaction mechanism of sulfite oxidase
- 2018
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 8:1
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Tidskriftsartikel (refereegranskat)abstract
- Sulfite oxidase is a mononuclear molybdenum enzyme that oxidises sulfite to sulfate in many organisms, including man. Three different reaction mechanisms have been suggested, based on experimental and computational studies. Here, we study all three with combined quantum mechanical (QM) and molecular mechanical (QM/MM) methods, including calculations with large basis sets, very large QM regions (803 atoms) and QM/MM free-energy perturbations. Our results show that the enzyme is set up to follow a mechanism in which the sulfur atom of the sulfite substrate reacts directly with the equatorial oxo ligand of the Mo ion, forming a Mo-bound sulfate product, which dissociates in the second step. The first step is rate limiting, with a barrier of 39-49 kJ/mol. The low barrier is obtained by an intricate hydrogen-bond network around the substrate, which is preserved during the reaction. This network favours the deprotonated substrate and disfavours the other two reaction mechanisms. We have studied the reaction with both an oxidised and a reduced form of the molybdopterin ligand and quantum-refinement calculations indicate that it is in the normal reduced tetrahydro form in this protein.
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| 2. |
- Ryde, Ulf, et al.
(författare)
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Computational Studies of Molybdenum and Tungsten Enzymes
- 2016. - 7
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Ingår i: Molybdenum and Tungsten Enzymes: Spectroscopic and Theoretical Investigations. - Cambridge : Royal Society of Chemistry. - 2045-547X. - 9781782628781 - 9781782628842 ; 2017-January:7, s. 275-321
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Bokkapitel (refereegranskat)abstract
- We review computational studies of three important mono-nuclear molybdenum oxo-transfer enzymes, dimethylsulfoxide reductase, sulfite oxidase and xanthine oxidase. We show that calculated energies for these reactions are very sensitive to details in the calculations, in particular to the density-functional method employed and the size of the basis set, but the treatment of dispersion and solvation effects is also crucial, as well as the definition of the reference state. We point out problems with standard quantum-mechanical (QM) cluster calculations, regarding the selection of the QM system and atomic coordinate constraints. Combined QM and molecular mechanics (QM/MM) methods also have important problems, which can be solved by calculations with very large QM systems (400-1000 atoms). Many studies have been published that reproduce experimentally measured activation energies, but for the wrong reason. We also compare the properties of molybdenum and tungsten and discuss why the active sites of the three families of molybdenum oxo-transfer enzymes are so different.
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