Dynamic evidence for metal ion catalysis in the reaction mediated by a flap endonuclease
| Autor: | Mark R. Tock, Jane A. Grasby, Elaine Frary, Jon R. Sayers |
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| Rok vydání: | 2003 |
| Předmět: |
Models
Molecular Metal ions in aqueous solution Inorganic chemistry Ionic bonding Biology General Biochemistry Genetics and Molecular Biology Catalysis Metal Reaction rate chemistry.chemical_compound Nucleophile Magnesium Molecular Biology Manganese General Immunology and Microbiology Molecular Structure General Neuroscience Leaving group Cobalt Articles Hydrogen-Ion Concentration Exodeoxyribonucleases chemistry Metals visual_art visual_art.visual_art_medium Hydroxide |
| Zdroj: | The EMBO journal. 22(5) |
| ISSN: | 0261-4189 |
| Popis: | On the basis of structural work, metal ions are proposed to play a catalytic role in reactions mediated by many phosphoryl transfer enzymes. To gain dynamic support for such mechanisms, the role of metal ion cofactors in phosphate diester hydrolysis catalysed by a flap endonuclease has been studied. The pH maximal rate profiles were measured in the presence of various metal ion cofactors; in each case, a single ionic form of the enzyme/cofactor accounts for the pH dependence. The kinetic pK(a)s display good correlation with the acidity of the corresponding hexahydrated metal ions, which strongly suggests a role for metal-bound hydroxide, or its equivalent ionic species, in the reaction. Comparing rates of reaction in the pH-independent regions, a small negative beta(nuc) value is observed. This suggests that expected trends in the nucleophilicity of the various metal-bound hydroxides are balanced by a second form of metal ion catalysis that is related to the acidity of the hexahydrated metal ion. This is likely to be either electrophilic catalysis or leaving group activation. |
| Databáze: | OpenAIRE |
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