| 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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Which functional groups of the molybdopterin ligand should be considered when modeling the active sites of the molybdenum and tungsten cofactors? A density functional theory study.
- 2009
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Ingår i: Journal of Biological Inorganic Chemistry. - : Springer Science and Business Media LLC. - 1432-1327 .- 0949-8257. ; 14:Online May 29, 2009, s. 1053-1064
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Tidskriftsartikel (refereegranskat)abstract
- A density functional theory study of the influence of the various functional groups of the molybdopterin ligand on electronic and geometric properties of active-site models for the molybdenum and tungsten cofactors has been undertaken. We used analogous molybdenum and tungsten complexes with increasingly accurate representation of the molybdopterin ligands and compared bond lengths, angles, charge distribution, composition of the binding orbitals, as well as the redox potentials in relation to each other. On the basis of our findings, we suggest using ligand systems including the pyrane and the pyrazine rings, besides the dithiolene function, to obtain sufficiently reliable computational, but also synthetic, models for the molybdenum and tungsten cofactors, whereas the second ring of the pterin might be neglected for efficiency reasons.
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| 3. |
- Van Severen, Marie-Céline, et al.
(författare)
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A quantum-mechanical study of the reaction mechanism of sulfite oxidase.
- 2014
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Ingår i: Journal of Biological Inorganic Chemistry. - : Springer Science and Business Media LLC. - 1432-1327 .- 0949-8257. ; 19:7, s. 1165-1179
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Tidskriftsartikel (refereegranskat)abstract
- The oxidation of sulfite to sulfate by two different models of the active site of sulfite oxidase has been studied. Both protonated and deprotonated substrates were tested. Geometries were optimized with density functional theory (TPSS/def2-SV(P)) and energies were calculated either with hybrid functionals and large basis sets (B3LYP/def2-TZVPD) including corrections for dispersion, solvation, and entropy, or with coupled-cluster theory (LCCSD(T0)) extrapolated toward a complete basis set. Three suggested reaction mechanisms have been compared and the results show that the lowest barriers are obtained for a mechanism where the substrate attacks a Mo-bound oxo ligand, directly forming a Mo-bound sulfate complex, which then dissociates into the products. Such a mechanism is more favorable than mechanisms involving a Mo-sulfite complex with the substrate coordinating either by the S or O atom. The activation energy is dominated by the Coulomb repulsion between the Mo complex and the substrate, which both have a negative charge of -1 or -2.
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