6XKA
TPX2 residues 7-20 fused to Aurora A residues 116-389 dephosphorylated, and CoAlated on C290
Summary for 6XKA
| Entry DOI | 10.2210/pdb6xka/pdb |
| Related | 6VPG 6VPH 6VPI 6VPJ 6VPL 6VPM |
| Descriptor | TPX2 fragment - Aurora A kinase domain fusion, COENZYME A (3 entities in total) |
| Functional Keywords | ser/thr kinase, transferase |
| Biological source | Homo sapiens (Human) More |
| Total number of polymer chains | 1 |
| Total formula weight | 34674.29 |
| Authors | Lim, D.C.,Yaffe, M.B. (deposition date: 2020-06-26, release date: 2020-08-05, Last modification date: 2023-10-18) |
| Primary citation | Lim, D.C.,Joukov, V.,Rettenmaier, T.J.,Kumagai, A.,Dunphy, W.G.,Wells, J.A.,Yaffe, M.B. Redox priming promotes Aurora A activation during mitosis. Sci.Signal., 13:-, 2020 Cited by PubMed Abstract: Cell cycle-dependent redox changes can mediate transient covalent modifications of cysteine thiols to modulate the activities of regulatory kinases and phosphatases. Our previously reported finding that protein cysteine oxidation is increased during mitosis relative to other cell cycle phases suggests that redox modifications could play prominent roles in regulating mitotic processes. The Aurora family of kinases and their downstream targets are key components of the cellular machinery that ensures the proper execution of mitosis and the accurate segregation of chromosomes to daughter cells. In this study, x-ray crystal structures of the Aurora A kinase domain delineate redox-sensitive cysteine residues that, upon covalent modification, can allosterically regulate kinase activity and oligomerization state. We showed in both egg extracts and mammalian cells that a conserved cysteine residue within the Aurora A activation loop is crucial for Aurora A activation by autophosphorylation. We further showed that covalent disulfide adducts of this residue promote autophosphorylation of the Aurora A kinase domain. These findings reveal a potential mechanistic link between Aurora A activation and changes in the intracellular redox state during mitosis and provide insights into how novel small-molecule inhibitors may be developed to target specific subpopulations of Aurora A. PubMed: 32694171DOI: 10.1126/scisignal.abb6707 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.65 Å) |
Structure validation
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