QM/MM Modeling of the Flavin Functionalization in the RutA Monooxygenase
Oxygenase activity of the flavin-dependent enzyme RutA is commonly associated with the formation of flavin-oxygen adducts in the enzyme active site. We report the results of quantum mechanics/molecular mechanics (QM/MM) modeling of possible reaction pathways initiated by various triplet state comple...
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| Format: | Article |
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MDPI AG
2023-03-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/28/5/2405 |
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| author | Bella Grigorenko Tatiana Domratcheva Alexander Nemukhin |
| author_facet | Bella Grigorenko Tatiana Domratcheva Alexander Nemukhin |
| author_sort | Bella Grigorenko |
| collection | DOAJ |
| description | Oxygenase activity of the flavin-dependent enzyme RutA is commonly associated with the formation of flavin-oxygen adducts in the enzyme active site. We report the results of quantum mechanics/molecular mechanics (QM/MM) modeling of possible reaction pathways initiated by various triplet state complexes of the molecular oxygen with the reduced flavin mononucleotide (FMN) formed in the protein cavities. According to the calculation results, these triplet-state flavin-oxygen complexes can be located at both <i>re</i>-side and <i>si</i>-side of the isoalloxazine ring of flavin. In both cases, the dioxygen moiety is activated by electron transfer from FMN, stimulating the attack of the arising reactive oxygen species at the C4a, N5, C6, and C8 positions in the isoalloxazine ring after the switch to the singlet state potential energy surface. The reaction pathways lead to the C(4a)-peroxide, N(5)-oxide, or C(6)-hydroperoxide covalent adducts or directly to the oxidized flavin, depending on the initial position of the oxygen molecule in the protein cavities. |
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| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-11T07:17:00Z |
| publishDate | 2023-03-01 |
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| series | Molecules |
| spelling | doaj.art-cdd13a03668841b3ab70b02b31e4f1f02023-11-17T08:16:12ZengMDPI AGMolecules1420-30492023-03-01285240510.3390/molecules28052405QM/MM Modeling of the Flavin Functionalization in the RutA MonooxygenaseBella Grigorenko0Tatiana Domratcheva1Alexander Nemukhin2Department of Chemistry, M.V. Lomonosov Moscow State University, Moscow 119991, RussiaDepartment of Chemistry, M.V. Lomonosov Moscow State University, Moscow 119991, RussiaDepartment of Chemistry, M.V. Lomonosov Moscow State University, Moscow 119991, RussiaOxygenase activity of the flavin-dependent enzyme RutA is commonly associated with the formation of flavin-oxygen adducts in the enzyme active site. We report the results of quantum mechanics/molecular mechanics (QM/MM) modeling of possible reaction pathways initiated by various triplet state complexes of the molecular oxygen with the reduced flavin mononucleotide (FMN) formed in the protein cavities. According to the calculation results, these triplet-state flavin-oxygen complexes can be located at both <i>re</i>-side and <i>si</i>-side of the isoalloxazine ring of flavin. In both cases, the dioxygen moiety is activated by electron transfer from FMN, stimulating the attack of the arising reactive oxygen species at the C4a, N5, C6, and C8 positions in the isoalloxazine ring after the switch to the singlet state potential energy surface. The reaction pathways lead to the C(4a)-peroxide, N(5)-oxide, or C(6)-hydroperoxide covalent adducts or directly to the oxidized flavin, depending on the initial position of the oxygen molecule in the protein cavities.https://www.mdpi.com/1420-3049/28/5/2405flavinmonooxygenasesRutA enzymemolecular oxygenquantum chemistryQM/MM |
| spellingShingle | Bella Grigorenko Tatiana Domratcheva Alexander Nemukhin QM/MM Modeling of the Flavin Functionalization in the RutA Monooxygenase Molecules flavin monooxygenases RutA enzyme molecular oxygen quantum chemistry QM/MM |
| title | QM/MM Modeling of the Flavin Functionalization in the RutA Monooxygenase |
| title_full | QM/MM Modeling of the Flavin Functionalization in the RutA Monooxygenase |
| title_fullStr | QM/MM Modeling of the Flavin Functionalization in the RutA Monooxygenase |
| title_full_unstemmed | QM/MM Modeling of the Flavin Functionalization in the RutA Monooxygenase |
| title_short | QM/MM Modeling of the Flavin Functionalization in the RutA Monooxygenase |
| title_sort | qm mm modeling of the flavin functionalization in the ruta monooxygenase |
| topic | flavin monooxygenases RutA enzyme molecular oxygen quantum chemistry QM/MM |
| url | https://www.mdpi.com/1420-3049/28/5/2405 |
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