Mechanism of DOPA radical generation and transfer in metal-free class Ie ribonucleotide reductase based on density functional theory
Quantum mechanical/molecular mechanical (QM/MM) calculations were carried out to investigate the mechanisms of the generation, transfer, and regeneration of the DOPA radical for metal-free class Ie ribonucleotide reductase. The crystal structure of MfR2 (Nature, 2018, 563, 416–420) was adopted for t...
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| Format: | Article |
| Language: | English |
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Elsevier
2022-01-01
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| Series: | Computational and Structural Biotechnology Journal |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2001037022000678 |
| _version_ | 1828088034873049088 |
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| author | Jinxin Zou Yao Chen Wei Feng |
| author_facet | Jinxin Zou Yao Chen Wei Feng |
| author_sort | Jinxin Zou |
| collection | DOAJ |
| description | Quantum mechanical/molecular mechanical (QM/MM) calculations were carried out to investigate the mechanisms of the generation, transfer, and regeneration of the DOPA radical for metal-free class Ie ribonucleotide reductase. The crystal structure of MfR2 (Nature, 2018, 563, 416–420) was adopted for the calculations. The QM/MM calculations have revealed several key points that are vital for understanding the mechanisms. The superoxide O2·− provided by the flavoprotein NrdI cannot directly oxidize the residue Tyr126 to the DOPA radical. It should be protonated to HO2·. The calculation results suggest that the covalent modification of Tyr126 and the DOPA radical generation can be carried out with no involvement of metal cofactors. This addresses the concerns of the articles (Nature, 2018, 563, 416–420; PNAS, 2018, 115, 10022–10027). Another concern from the articles is that how the DOPA radical is transferred from the radical trap. The DFT calculations have demonstrated that Lys213 is a key residue for the radical transfer from the DOPA radical. The ε-amino group of Lys213 is used not only as a bridge for the electron transfer but also as a proton donor. It can provide a proton to DOPA126 via a water molecule, and thus the radical transfer from DOPA126 to Trp52 is facilitated. It has also been revealed that the protonation of Asp88 is the prerequisite for the DOPA radical generation and the radical transfer in class Ie. Once the radical is quenched, it can be regenerated via the oxidations by superoxide O2·− and hydroperoxyl radical HO2·. |
| first_indexed | 2024-04-11T05:20:19Z |
| format | Article |
| id | doaj.art-4b7cb0ac99e248f1a10a457b55617d1f |
| institution | Directory Open Access Journal |
| issn | 2001-0370 |
| language | English |
| last_indexed | 2024-04-11T05:20:19Z |
| publishDate | 2022-01-01 |
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| record_format | Article |
| series | Computational and Structural Biotechnology Journal |
| spelling | doaj.art-4b7cb0ac99e248f1a10a457b55617d1f2022-12-24T04:51:37ZengElsevierComputational and Structural Biotechnology Journal2001-03702022-01-012011111131Mechanism of DOPA radical generation and transfer in metal-free class Ie ribonucleotide reductase based on density functional theoryJinxin Zou0Yao Chen1Wei Feng2Department of Biological Engineering, Beijing University of Chemical Technology, Beijing 100029, ChinaDepartment of Biological Engineering, Beijing University of Chemical Technology, Beijing 100029, ChinaCorresponding author.; Department of Biological Engineering, Beijing University of Chemical Technology, Beijing 100029, ChinaQuantum mechanical/molecular mechanical (QM/MM) calculations were carried out to investigate the mechanisms of the generation, transfer, and regeneration of the DOPA radical for metal-free class Ie ribonucleotide reductase. The crystal structure of MfR2 (Nature, 2018, 563, 416–420) was adopted for the calculations. The QM/MM calculations have revealed several key points that are vital for understanding the mechanisms. The superoxide O2·− provided by the flavoprotein NrdI cannot directly oxidize the residue Tyr126 to the DOPA radical. It should be protonated to HO2·. The calculation results suggest that the covalent modification of Tyr126 and the DOPA radical generation can be carried out with no involvement of metal cofactors. This addresses the concerns of the articles (Nature, 2018, 563, 416–420; PNAS, 2018, 115, 10022–10027). Another concern from the articles is that how the DOPA radical is transferred from the radical trap. The DFT calculations have demonstrated that Lys213 is a key residue for the radical transfer from the DOPA radical. The ε-amino group of Lys213 is used not only as a bridge for the electron transfer but also as a proton donor. It can provide a proton to DOPA126 via a water molecule, and thus the radical transfer from DOPA126 to Trp52 is facilitated. It has also been revealed that the protonation of Asp88 is the prerequisite for the DOPA radical generation and the radical transfer in class Ie. Once the radical is quenched, it can be regenerated via the oxidations by superoxide O2·− and hydroperoxyl radical HO2·.http://www.sciencedirect.com/science/article/pii/S2001037022000678Density functional theoryClass Ie RNRDOPA radicalRadical transferSuperoxide |
| spellingShingle | Jinxin Zou Yao Chen Wei Feng Mechanism of DOPA radical generation and transfer in metal-free class Ie ribonucleotide reductase based on density functional theory Computational and Structural Biotechnology Journal Density functional theory Class Ie RNR DOPA radical Radical transfer Superoxide |
| title | Mechanism of DOPA radical generation and transfer in metal-free class Ie ribonucleotide reductase based on density functional theory |
| title_full | Mechanism of DOPA radical generation and transfer in metal-free class Ie ribonucleotide reductase based on density functional theory |
| title_fullStr | Mechanism of DOPA radical generation and transfer in metal-free class Ie ribonucleotide reductase based on density functional theory |
| title_full_unstemmed | Mechanism of DOPA radical generation and transfer in metal-free class Ie ribonucleotide reductase based on density functional theory |
| title_short | Mechanism of DOPA radical generation and transfer in metal-free class Ie ribonucleotide reductase based on density functional theory |
| title_sort | mechanism of dopa radical generation and transfer in metal free class ie ribonucleotide reductase based on density functional theory |
| topic | Density functional theory Class Ie RNR DOPA radical Radical transfer Superoxide |
| url | http://www.sciencedirect.com/science/article/pii/S2001037022000678 |
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