4C3R
Structure of dephosphorylated Aurora A (122-403) bound to AMPPCP
Summary for 4C3R
| Entry DOI | 10.2210/pdb4c3r/pdb |
| Related | 4C3P |
| Descriptor | AURORA KINASE A, PHOSPHOMETHYLPHOSPHONIC ACID ADENYLATE ESTER (2 entities in total) |
| Functional Keywords | transferase, aurora a, activation, cell cycle, cancer |
| Biological source | HOMO SAPIENS (HUMAN) |
| Total number of polymer chains | 1 |
| Total formula weight | 33194.67 |
| Authors | Zorba, A.,Kutter, S.,Cho, Y.-J.,Kern, D. (deposition date: 2013-08-26, release date: 2014-05-28, Last modification date: 2023-12-20) |
| Primary citation | Zorba, A.,Buosi, V.,Kutter, S.,Kern, N.,Pontiggia, F.,Cho, Y.J.,Kern, D. Molecular Mechanism of Aurora a Kinase Autophosphorylation and its Allosteric Activation by Tpx2. Elife, 3:02667-, 2014 Cited by PubMed Abstract: We elucidate the molecular mechanisms of two distinct activation strategies (autophosphorylation and TPX2-mediated activation) in human Aurora A kinase. Classic allosteric activation is in play where either activation loop phosphorylation or TPX2 binding to a conserved hydrophobic groove shifts the equilibrium far towards the active conformation. We resolve the controversy about the mechanism of autophosphorylation by demonstrating intermolecular autophosphorylation in a long-lived dimer by combining X-ray crystallography with functional assays. We then address the allosteric activation by TPX2 through activity assays and the crystal structure of a domain-swapped dimer of dephosphorylated Aurora A and TPX2(1-25). While autophosphorylation is the key regulatory mechanism in the centrosomes in the early stages of mitosis, allosteric activation by TPX2 of dephosphorylated Aurora A could be at play in the spindle microtubules. The mechanistic insights into autophosphorylation and allosteric activation by TPX2 binding proposed here, may have implications for understanding regulation of other protein kinases.DOI: http://dx.doi.org/10.7554/eLife.02667.001. PubMed: 24867643DOI: 10.7554/ELIFE.02667 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.79 Å) |
Structure validation
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