Linked Life Data

16774919

Source:http://linkedlifedata.com/resource/pubmed/id/16774919

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
33
pubmed:dateCreated
2006-8-14
pubmed:abstractText
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 Mg2+ cations in an unusual, bent geometry. The Mg2+ cations play a structural role and are thought to also participate catalytically in the enzyme reaction. Co-binding of the ATP x Mg3(2+) complex was shown recently to increase the Asp/Asn binding free energy difference, indicating that amino acid discrimination is substrate-assisted. Here, we used molecular dynamics free energy simulations and continuum electrostatic calculations to resolve two related questions. First, we showed that if one of the Mg2+ cations is removed, the Asp/Asn binding specificity is strongly reduced. Second, we computed the relative stabilities of the three-cation complex and the 2-cation complexes. We found that the 3-cation complex is overwhelmingly favored at ordinary magnesium concentrations, so that the protein is protected against the 2-cation state. In the homologous LysRS, the 3-cation complex was also strongly favored, but the third cation did not affect Lys binding. In tRNA-bound AspRS, the single remaining Mg2+ cation strongly favored the Asp-adenylate substrate relative to Asn-adenylate. Thus, in addition to their structural and catalytic roles, the Mg2+ cations contribute to specificity in AspRS through long range electrostatic interactions with the Asp side chain in both the pre- and post-adenylation states.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
18
pubmed:volume
281
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
23792-803
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:16774919-Adenosine Monophosphate, pubmed-meshheading:16774919-Adenosine Triphosphate, pubmed-meshheading:16774919-Aminoacylation, pubmed-meshheading:16774919-Archaeal Proteins, pubmed-meshheading:16774919-Asparagine, pubmed-meshheading:16774919-Aspartate-tRNA Ligase, pubmed-meshheading:16774919-Aspartic Acid, pubmed-meshheading:16774919-Binding Sites, pubmed-meshheading:16774919-Catalysis, pubmed-meshheading:16774919-Cations, Divalent, pubmed-meshheading:16774919-Computer Simulation, pubmed-meshheading:16774919-Crystallography, X-Ray, pubmed-meshheading:16774919-Enzyme Stability, pubmed-meshheading:16774919-Magnesium, pubmed-meshheading:16774919-Pyrococcus, pubmed-meshheading:16774919-RNA, Transfer, pubmed-meshheading:16774919-Static Electricity, pubmed-meshheading:16774919-Substrate Specificity, pubmed-meshheading:16774919-Thermodynamics
pubmed:year
2006
pubmed:articleTitle
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.
pubmed:affiliation
Laboratoire de Biochimie, CNRS, UMR7654, Department of Biology, Ecole Polytechnique, 91128 Palaiseau, France.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Validation Studies