4L1B

Crystal Structure of p110alpha complexed with niSH2 of p85alpha

4L1B の概要

• エントリーDOI: 10.2210/pdb4l1b/pdb
• 関連するPDBエントリー: 4L23 4L2Y
• 分子名称: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform, Phosphatidylinositol 3-kinase regulatory subunit alpha, SULFATE ION, ... (4 entities in total)
• 機能のキーワード: atp binding, signaling protein-transferase-inhibitor complex, signaling protein/transferase/inhibitor
• 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: 163592.53

構造登録者

Zhang, J.,Zhao, Y.L.,Chen, Y.Y.,Huang, M.,Jiang, F. (登録日: 2013-06-03, 公開日: 2014-01-01, 最終更新日: 2023-09-20)

主引用文献

Zhao, Y.,Zhang, X.,Chen, Y.,Lu, S.,Peng, Y.,Wang, X.,Guo, C.,Zhou, A.,Zhang, J.,Luo, Y.,Shen, Q.,Ding, J.,Meng, L.,Zhang, J.
Crystal Structures of PI3K alpha Complexed with PI103 and Its Derivatives: New Directions for Inhibitors Design.
ACS Med Chem Lett, 5:138-142, 2014

PubMed Abstract: The phosphatidylinositol 3-kinase (PI3K) signaling pathway plays important roles in cell proliferation, growth, and survival. Hyperactivated PI3K is frequently found in a wide variety of human cancers, validating it as a promising target for cancer therapy. We determined the crystal structure of the human PI3Kα-PI103 complex to unravel molecular interactions. Based on the structure, substitution at the R1 position of the phenol portion of PI103 was demonstrated to improve binding affinity via forming a new H-bond with Lys802 at the bottom of the ATP catalytic site. Interestingly, the crystal structure of the PI3Kα-9d complex revealed that the flexibility of Lys802 can also induce additional space at the catalytic site for further modification. Thus, these crystal structures provide a molecular basis for the strong and specific interactions and demonstrate the important role of Lys802 in the design of novel PI3Kα inhibitors.

PubMed: 24900786
DOI: 10.1021/ml400378e

実験手法

X-RAY DIFFRACTION (2.586 Å)