Author ORCID Identifier
https://orcid.org/0000-0002-2956-9781
Document Type
Article
Publication Date
2012
Publication Title
The Journal of Physical Chemistry
Volume
116
Issue
17
First Page
5205
Last Page
5212
Abstract
The structure and nature of the fully bound active site of Threonyl-tRNA Synthetase (ThrRS) for the second half-reaction has been investigated using molecular dynamics simulations. More specifically, we examined the ThrRS active site with both the substrate Threonyl-AMP and the cosubstrate cognate Threonyl-tRNA bound. Furthermore, we also considered the cases in which an active-site histidyl residue (His309) is either neutral or protonated. Moreover, we considered the role a water molecule may play in formation of a viable Michaelis complex. From the results it is found that the most likely role of His309 is in binding and properly orientating the ribose of the Ado76 nucleotidyl residue of the threonyl-tRNA via formation of a direct His309···Ado76 hydrogen bond, i.e., without involvement of a water. In addition, the imidazole of the His309 residue is likely neutral. It was found that upon protonation the positioning of the Ado76-3′-OH was perturbed, leading to a reduced chance for nucleophilic attack of the threonyl’s C1 center.
DOI
10.1021/jp302556e
Recommended Citation
Bushnell, Eric Andre; Huang, WenJuan; Llano, Jorge; and Gauld, James. (2012). Molecular Dynamics Investigation into Substrate Binding and Identity of the Catalytic Base in the Mechanism of Threonyl-tRNA Synthetase. The Journal of Physical Chemistry, 116 (17), 5205-5212.
https://scholar.uwindsor.ca/chemistrybiochemistrypub/123