Mechanistic study on DNA mutation of the cytosine methylation reaction at C5 position
DNA methylation is a crucial epigenetic mark connected to conventionally changing the DNA bases, typically by adding methyl groups into DNA bases. Methylation of cytosine at the C5 position (5-methylcytosine) occurs mostly in the context of cytosine-phosphate-guanine dinucleotides, the methylation o...
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| Format: | Article |
| Language: | English |
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Elsevier
2022-08-01
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| Series: | Arabian Journal of Chemistry |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S1878535222002726 |
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| author | Mansour H. Almatarneh Ghada G. Kayed Sanaa S. Al Abbad Zainab H.A. Alsunaidi Mohammed S. Al-Sheraideh Yuming Zhao |
| author_facet | Mansour H. Almatarneh Ghada G. Kayed Sanaa S. Al Abbad Zainab H.A. Alsunaidi Mohammed S. Al-Sheraideh Yuming Zhao |
| author_sort | Mansour H. Almatarneh |
| collection | DOAJ |
| description | DNA methylation is a crucial epigenetic mark connected to conventionally changing the DNA bases, typically by adding methyl groups into DNA bases. Methylation of cytosine at the C5 position (5-methylcytosine) occurs mostly in the context of cytosine-phosphate-guanine dinucleotides, the methylation of which has important impacts on gene regulation and expression. However, the mechanistic details of this reaction are still debatable concerning the concertedness of the key reaction steps and the roles played by the base that abstracts the proton in the β-elimination and water molecules at the active site. To gain a deeper insight into the formation of 5-mehtylcytosine, an extensive density functional theory (DFT) study was performed with the B3LYP functional in conjunction with different basis sets. Our study has clearly established the mechanistic details of this methylation approach, based on which the roles of conserved active site residues, such as glutamic acid and waters, are well understood. Our results show that the reaction of 5-methylcytosine follows a concerted mechanism in which water molecules are critically involved. Moreover, arginine and alanine give more significant catalytic effects than glutamic acid on the 5-methylcytosine process. Considering the effect of Alanine, Arginine, and one water bridging molecule, the activation energy is 31 kJ mol−1 calculated at B3LYP/6-31G(d) level of theory. |
| first_indexed | 2024-04-13T22:02:12Z |
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| institution | Directory Open Access Journal |
| issn | 1878-5352 |
| language | English |
| last_indexed | 2024-04-13T22:02:12Z |
| publishDate | 2022-08-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Arabian Journal of Chemistry |
| spelling | doaj.art-8c9ae837da274776a43b0c0cb75662782022-12-22T02:28:03ZengElsevierArabian Journal of Chemistry1878-53522022-08-01158103956Mechanistic study on DNA mutation of the cytosine methylation reaction at C5 positionMansour H. Almatarneh0Ghada G. Kayed1Sanaa S. Al Abbad2Zainab H.A. Alsunaidi3Mohammed S. Al-Sheraideh4Yuming Zhao5Department of Chemistry, University of Jordan, Amman 11942, Jordan; Department of Chemistry, Memorial University, St. John’s NL A1B 3X7, Canada; Corresponding authors at: Department of Chemistry, University of Jordan, Amman 11942, Jordan (M.H. Almatarneh). Department of Chemistry, Memorial University, St. John’s, NL A1B 3X7, Canada (Y. Zhao).Department of Chemistry, University of Jordan, Amman 11942, JordanDepartment of Chemistry, College of Science, Imam Abdulrahman Bin Faisal University, Dammam 31441, Saudi ArabiaDepartment of Chemistry, College of Science, Imam Abdulrahman Bin Faisal University, Dammam 31441, Saudi ArabiaDepartment of Chemistry, College of Science, Imam Abdulrahman Bin Faisal University, Dammam 31441, Saudi ArabiaDepartment of Chemistry, Memorial University, St. John’s NL A1B 3X7, Canada; Corresponding authors at: Department of Chemistry, University of Jordan, Amman 11942, Jordan (M.H. Almatarneh). Department of Chemistry, Memorial University, St. John’s, NL A1B 3X7, Canada (Y. Zhao).DNA methylation is a crucial epigenetic mark connected to conventionally changing the DNA bases, typically by adding methyl groups into DNA bases. Methylation of cytosine at the C5 position (5-methylcytosine) occurs mostly in the context of cytosine-phosphate-guanine dinucleotides, the methylation of which has important impacts on gene regulation and expression. However, the mechanistic details of this reaction are still debatable concerning the concertedness of the key reaction steps and the roles played by the base that abstracts the proton in the β-elimination and water molecules at the active site. To gain a deeper insight into the formation of 5-mehtylcytosine, an extensive density functional theory (DFT) study was performed with the B3LYP functional in conjunction with different basis sets. Our study has clearly established the mechanistic details of this methylation approach, based on which the roles of conserved active site residues, such as glutamic acid and waters, are well understood. Our results show that the reaction of 5-methylcytosine follows a concerted mechanism in which water molecules are critically involved. Moreover, arginine and alanine give more significant catalytic effects than glutamic acid on the 5-methylcytosine process. Considering the effect of Alanine, Arginine, and one water bridging molecule, the activation energy is 31 kJ mol−1 calculated at B3LYP/6-31G(d) level of theory.http://www.sciencedirect.com/science/article/pii/S1878535222002726EpigeneticsDNA MethylationDNA Methyltransferases5-Methyl CytosineCpG methylationTransition state |
| spellingShingle | Mansour H. Almatarneh Ghada G. Kayed Sanaa S. Al Abbad Zainab H.A. Alsunaidi Mohammed S. Al-Sheraideh Yuming Zhao Mechanistic study on DNA mutation of the cytosine methylation reaction at C5 position Arabian Journal of Chemistry Epigenetics DNA Methylation DNA Methyltransferases 5-Methyl Cytosine CpG methylation Transition state |
| title | Mechanistic study on DNA mutation of the cytosine methylation reaction at C5 position |
| title_full | Mechanistic study on DNA mutation of the cytosine methylation reaction at C5 position |
| title_fullStr | Mechanistic study on DNA mutation of the cytosine methylation reaction at C5 position |
| title_full_unstemmed | Mechanistic study on DNA mutation of the cytosine methylation reaction at C5 position |
| title_short | Mechanistic study on DNA mutation of the cytosine methylation reaction at C5 position |
| title_sort | mechanistic study on dna mutation of the cytosine methylation reaction at c5 position |
| topic | Epigenetics DNA Methylation DNA Methyltransferases 5-Methyl Cytosine CpG methylation Transition state |
| url | http://www.sciencedirect.com/science/article/pii/S1878535222002726 |
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