6VPM

TPX2 residues 7-20 fused to Aurora A residues 116-389 with C290 disulfide bonded to compound 8-34, and in complex with AMP-PNP

6VPM の概要

• エントリーDOI: 10.2210/pdb6vpm/pdb
• 分子名称: TPX2 fragment - Aurora A kinase domain fusion, MAGNESIUM ION, ADENOSINE MONOPHOSPHATE, ... (6 entities in total)
• 機能のキーワード: ser/thr kinase, transferase
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 69671.49

構造登録者

Lim, D.C.,Yaffe, M.B. (登録日: 2020-02-03, 公開日: 2020-08-05, 最終更新日: 2024-10-09)

主引用文献

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

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: 32694171
DOI: 10.1126/scisignal.abb6707

実験手法

X-RAY DIFFRACTION (1.58 Å)