Molecular dynamics simulations show that bound Mg2+ contributes to amino acid and aminoacyl adenylate binding specificity in aspartyl-tRNA synthetase through long-range electrostatic interactions.
| Related Articles |
Molecular dynamics simulations show that bound Mg2+ contributes to amino acid and aminoacyl adenylate binding specificity in aspartyl-tRNA synthetase through long-range electrostatic interactions.
J Biol Chem. 2006 Jun 14;
Authors: Thompson D, Simonson T
Molecular recognition between the aminoacyl-tRNA synthetase enzymes and their cognate amino acid ligands is essential for the faithful translation of the genetic code. In aspartyl-tRNA synthetase (AspRS), the co-substrate ATP binds preferentially with three associated Mg(2+) cations, in an unusual, bent geometry. The Mg(2+) cations play a structural role and are thought to also participate catalytically in the enzyme reaction. Co-binding of the ATP:Mg(2+)(3) complex was shown recently to increase the Asp/Asn binding free energy difference, indicating that amino acid discrimination is substrate-assisted. Here, we use molecular dynamics free energy simulations and continuum electrostatic calculations to resolve three related questions. First, we show that if one of the Mg(2+) cations is removed, the Asp/Asn binding specificity is strongly reduced. Second, we compute the relative stabilities of the three-cation complex and the two-cation complexes. We find that the three-cation complex is overwhelmingly favoured at ordinary magnesium concentrations, so that the protein is protected against the two-cation state. In the homologous LysRS, the three-cation complex is also strongly favoured, but the third cation does not affect Lys binding. Finally, in tRNA-bound AspRS, the single remaining Mg(2+) cation strongly favours the Asp-adenylate substrate, relative to Asn-adenylate. Thus, in addition to their structural and catalytic roles, the Mg(2+) cations contribute to specificity in AspRS, through long-range electrostatic interactions with the Asp sidechain in both the pre- and post-adenylation states.
PMID: 16774919 [PubMed - as supplied by publisher]
Related posts:
- Bangladeshi medicinal plant extracts inhibiting molecular interactions between nuclear factors and target DNA sequences mimicking NF-kappaB binding sites.
- Molecular simulations reveal a new entry site in quercetin 2,3-dioxygenase. A pathway for dioxygen?
- 4-hydroxyisoleucine an unusual amino acid as antidyslipidemic and antihyperglycemic agent.
- Ribokinase from E. coli: Expression, purification, and substrate specificity.
- Amino Acid, Mineral and Fatty Acid Content of Pumpkin Seeds (Cucurbita spp) and Cyperus esculentus Nuts in the Republic of Niger.