| http://purl.uniprot.org/citations/23082977 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/23082977 | http://www.w3.org/2000/01/rdf-schema#comment | "Protein kinases, which play an important role in the regulation of the majority of cellular processes, especially those involved in cellular signal transduction, by catalyzing the phosphorylation of specific proteins, are the attractive targets of drug design in pharmaceuticals industry. Interestingly, up to 10% of proteins in the human kinome termed pseudokinases are predicted to be enzymatically inactive, but are still pivotal in regulating diverse cellular processes and thus may be a potential therapeutic target to a certain extent. To study the underlying molecular mechanisms, molecular dynamics simulations were performed to investigate the role of bivalent cations Mg²⁺ and Mn²⁺ in the structural stabilities and dynamical behaviors of vaccinia related kinase 3 (VRK3), which was the first solved crystal structure of the pseudokinase, and that of its closest active relatives VRK1 and VRK2. Toward this end, a series of molecular dynamics simulations have been performed with different divalent cations binding modes in the active site. The simulations suggested that the binding of Mg²⁺ in the active site played a key structural role in the stabilization of VRK1 and VRK2, and Mn²⁺ was slightly required for VRK2. By contrast, the pseudokinase VRK3 was well ordered with lower RMSD values indicating it was rigid and very stable regardless of whether the bivalent cations were bound or not during the simulations. The present study provided evidence for the role of bivalent cations in structural stabilities of VRKs and the proposed simulation model reconciled the interpretation of available experimental structural and thermal denaturation assay data. These results gave us further information on the dynamical behaviors of the active site of VRKs and suggested a mechanism of regulation of their structural stabilities, and might provide a starting point for the more detailed follow-up investigation of drug design."xsd:string |
| http://purl.uniprot.org/citations/23082977 | http://purl.org/dc/terms/identifier | "doi:10.2174/1381612811319120014"xsd:string |
| http://purl.uniprot.org/citations/23082977 | http://purl.uniprot.org/core/author | "Li G."xsd:string |
| http://purl.uniprot.org/citations/23082977 | http://purl.uniprot.org/core/author | "Zhang J."xsd:string |
| http://purl.uniprot.org/citations/23082977 | http://purl.uniprot.org/core/author | "Ren H."xsd:string |
| http://purl.uniprot.org/citations/23082977 | http://purl.uniprot.org/core/author | "Ren P."xsd:string |
| http://purl.uniprot.org/citations/23082977 | http://purl.uniprot.org/core/author | "Fu T."xsd:string |
| http://purl.uniprot.org/citations/23082977 | http://purl.uniprot.org/core/author | "Enyedy I."xsd:string |
| http://purl.uniprot.org/citations/23082977 | http://purl.uniprot.org/core/date | "2013"xsd:gYear |
| http://purl.uniprot.org/citations/23082977 | http://purl.uniprot.org/core/name | "Curr Pharm Des"xsd:string |
| http://purl.uniprot.org/citations/23082977 | http://purl.uniprot.org/core/pages | "2269-2281"xsd:string |
| http://purl.uniprot.org/citations/23082977 | http://purl.uniprot.org/core/title | "Role of bivalent cations in structural stabilities of new drug targets--vaccinia-related kinases (VRK) from molecular dynamics simulations."xsd:string |
| http://purl.uniprot.org/citations/23082977 | http://purl.uniprot.org/core/volume | "19"xsd:string |
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