A Divalent Metal Ion-Dependent N 1 -Methyl Transfer to G37-tRNA
| Autor: | Thomas Christian, Georges Lahoud, Reiko Sakaguchi, Howard Gamper, Ya-Ming Hou |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
S-Adenosylmethionine
Stereochemistry Sulfonium Clinical Biochemistry Inorganic chemistry Kinetics Biochemistry Article Catalysis Metal chemistry.chemical_compound RNA Transfer Nucleophile Drug Discovery Escherichia coli Magnesium Molecular Biology Ions Pharmacology tRNA Methyltransferases Chemistry Escherichia coli Proteins Substrate (chemistry) General Medicine Hydrogen-Ion Concentration TRNA Methyltransferases Metals Biocatalysis visual_art visual_art.visual_art_medium Molecular Medicine |
| Zdroj: | Chemistry & Biology. 21:1351-1360 |
| ISSN: | 1074-5521 |
| DOI: | 10.1016/j.chembiol.2014.07.023 |
| Popis: | Summary The catalytic mechanism of the majority of S -adenosyl methionine (AdoMet)-dependent methyl transferases requires no divalent metal ions. Here we report that methyl transfer from AdoMet to N 1 of G37-tRNA, catalyzed by the bacterial TrmD enzyme, is strongly dependent on divalent metal ions and that Mg 2+ is the most physiologically relevant. Kinetic isotope analysis, metal rescue, and spectroscopic measurements indicate that Mg 2+ is not involved in substrate binding, but in promoting methyl transfer. On the basis of the pH-activity profile indicating one proton transfer during the TrmD reaction, we propose a catalytic mechanism in which the role of Mg 2+ is to help to increase the nucleophilicity of N 1 of G37 and stabilize the negative developing charge on O 6 during attack on the methyl sulfonium of AdoMet. This work demonstrates how Mg 2+ contributes to the catalysis of AdoMet-dependent methyl transfer in one of the most crucial posttranscriptional modifications to tRNA. |
| Databáze: | OpenAIRE |
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