| http://purl.uniprot.org/citations/21347367 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/21347367 | http://www.w3.org/2000/01/rdf-schema#comment | "Aurora A is an important oncogenic kinase for mitotic spindle assembly and a potentially attractive target for human cancers. Its activation could be regulated by ATP cycle and its activator TPX2. To understand the activation mechanism of Aurora A, a series of 20 ns molecular dynamics (MD) simulations were performed on both the wild-type kinase and its mutants. Analyzing the three dynamic trajectories (Aurora A-ATP, Aurora A-ADP, and Aurora A-ADP-TPX2) at the residue level, for the first time we find two TPX2-dependent switches, i.e., switch-1 (Lys-143) and switch-2 (Arg-180), which are tightly associated with Aurora A activation. In the absence of TPX2, Lys-143 exhibits a "closed" state, and becomes hydrogen-bonded to ADP. Once TPX2 binding occurs, switch-1 is forced to "open" the binding site, thus pulling ADP away from Aurora A. Without facilitation of TPX2, switch-2 exits in an "open" conformation which accompanies the outward-flipping movement of P·Thr288 (in an inactive conformation), leading to the crucial phosphothreonine exposed and accessible for deactivation. However, with the binding of TPX2, switch-2 is forced to undergo a "closed" movement, thus capturing P·Thr288 into a buried position and locking its active conformation. Analysis of two Aurora A (K143A and R180A) mutants for the two switches further verifies their functionality and reliability in controlling Aurora activity. Our systems therefore suggest two switches determining Aurora A activation, which are important for the development of aurora kinase inhibitors."xsd:string |
| http://purl.uniprot.org/citations/21347367 | http://purl.org/dc/terms/identifier | "doi:10.1371/journal.pone.0016757"xsd:string |
| http://purl.uniprot.org/citations/21347367 | http://purl.uniprot.org/core/author | "Li Y."xsd:string |
| http://purl.uniprot.org/citations/21347367 | http://purl.uniprot.org/core/author | "Wang Y."xsd:string |
| http://purl.uniprot.org/citations/21347367 | http://purl.uniprot.org/core/author | "Wang X."xsd:string |
| http://purl.uniprot.org/citations/21347367 | http://purl.uniprot.org/core/author | "Xu X."xsd:string |
| http://purl.uniprot.org/citations/21347367 | http://purl.uniprot.org/core/author | "Xiao Z."xsd:string |
| http://purl.uniprot.org/citations/21347367 | http://purl.uniprot.org/core/date | "2011"xsd:gYear |
| http://purl.uniprot.org/citations/21347367 | http://purl.uniprot.org/core/name | "PLoS One"xsd:string |
| http://purl.uniprot.org/citations/21347367 | http://purl.uniprot.org/core/pages | "e16757"xsd:string |
| http://purl.uniprot.org/citations/21347367 | http://purl.uniprot.org/core/title | "Two TPX2-dependent switches control the activity of Aurora A."xsd:string |
| http://purl.uniprot.org/citations/21347367 | http://purl.uniprot.org/core/volume | "6"xsd:string |
| http://purl.uniprot.org/citations/21347367 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/21347367 |
| http://purl.uniprot.org/citations/21347367 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/21347367 |
| http://purl.uniprot.org/uniprot/#_Q14203-mappedCitation-21347367 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/21347367 |
| http://purl.uniprot.org/uniprot/#_Q14204-mappedCitation-21347367 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/21347367 |
| http://purl.uniprot.org/uniprot/#_A8K8P3-mappedCitation-21347367 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/21347367 |
| http://purl.uniprot.org/uniprot/#_B3KM90-mappedCitation-21347367 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/21347367 |
| http://purl.uniprot.org/uniprot/#_B2R6Z3-mappedCitation-21347367 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/21347367 |
| http://purl.uniprot.org/uniprot/#_B4DX16-mappedCitation-21347367 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/21347367 |
| http://purl.uniprot.org/uniprot/#_P51955-mappedCitation-21347367 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/21347367 |
| http://purl.uniprot.org/uniprot/#_Q7Z7A1-mappedCitation-21347367 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/21347367 |
| http://purl.uniprot.org/uniprot/#_Q13561-mappedCitation-21347367 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/21347367 |
| http://purl.uniprot.org/uniprot/#_O75935-mappedCitation-21347367 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/21347367 |