دورية أكاديمية
Role of Water in Proton-Coupled Electron Transfer between Tyrosine and Cysteine in Ribonucleotide Reductase.
| العنوان: | Role of Water in Proton-Coupled Electron Transfer between Tyrosine and Cysteine in Ribonucleotide Reductase. |
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| المؤلفون: | Zhong J; Department of Chemistry, Yale University, 225 Prospect Street, New Haven, Connecticut 06520, United States., Reinhardt CR; Department of Molecular Biophysics & Biochemistry, Yale University, 266 Whitney Avenue, New Haven, Connecticut 06520, United States., Hammes-Schiffer S; Department of Chemistry, Yale University, 225 Prospect Street, New Haven, Connecticut 06520, United States. |
| المصدر: | Journal of the American Chemical Society [J Am Chem Soc] 2022 Apr 27; Vol. 144 (16), pp. 7208-7214. Date of Electronic Publication: 2022 Apr 15. |
| نوع المنشور: | Journal Article; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, N.I.H., Extramural |
| اللغة: | English |
| بيانات الدورية: | Publisher: American Chemical Society Country of Publication: United States NLM ID: 7503056 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1520-5126 (Electronic) Linking ISSN: 00027863 NLM ISO Abbreviation: J Am Chem Soc Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Washington, DC : American Chemical Society Original Publication: Easton, Pa. [etc.] |
| مواضيع طبية MeSH: | Ribonucleotide Reductases*/chemistry, Cysteine/metabolism ; Electron Transport ; Electrons ; Escherichia coli/metabolism ; Free Radicals/chemistry ; Glutamic Acid/chemistry ; Models, Molecular ; Protons ; Tyrosine/chemistry ; Water |
| مستخلص: | Ribonucleotide reductase (RNR) catalyzes the reduction of ribonucleotides to deoxyribonucleotides and is critical for DNA synthesis and repair in all organisms. Its mechanism requires radical transfer along a ∼32 Å pathway through a series of proton-coupled electron transfer (PCET) steps. Previous simulations suggested that a glutamate residue (E623) mediates the PCET reaction between two stacked tyrosine residues (Y730 and Y731) through a proton relay mechanism. This work focuses on the adjacent PCET reaction between Y730 and a cysteine residue (C439). Quantum mechanical/molecular mechanical free energy simulations illustrate that when Y730 and Y731 are stacked, E623 stabilizes the radical on C439 through hydrogen bonding with the Y730 hydroxyl group. When Y731 is flipped away from Y730, a water molecule stabilizes the radical on C439 through hydrogen bonding with Y730 and lowers the free energy barrier for radical transfer from Y730 to C439 through electrostatic interactions with the transferring hydrogen but does not directly accept the proton. These simulations indicate that the conformational motions and electrostatic interactions of the tyrosines, cysteine, glutamate, and water strongly impact the thermodynamics and kinetics of these two coupled PCET reactions. Such insights are important for protein engineering efforts aimed at altering radical transfer in RNR. |
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| معلومات مُعتمدة: | R35 GM139449 United States GM NIGMS NIH HHS |
| المشرفين على المادة: | 0 (Free Radicals) 0 (Protons) 059QF0KO0R (Water) 3KX376GY7L (Glutamic Acid) 42HK56048U (Tyrosine) EC 1.17.4.- (Ribonucleotide Reductases) K848JZ4886 (Cysteine) |
| تواريخ الأحداث: | Date Created: 20220415 Date Completed: 20220428 Latest Revision: 20230428 |
| رمز التحديث: | 20240628 |
| مُعرف محوري في PubMed: | PMC9197590 |
| DOI: | 10.1021/jacs.1c13455 |
| PMID: | 35426309 |
| قاعدة البيانات: | MEDLINE |
Find this issue from the American Chemical Society | تدمد: | 1520-5126 |
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| DOI: | 10.1021/jacs.1c13455 |