5XGH

Crystal structure of PI3K complex with an inhibitor

Summary for 5XGH

• Entry DOI: 10.2210/pdb5xgh/pdb
• Related: 5XGI 5XGJ
• Descriptor: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform, Phosphatidylinositol 3-kinase regulatory subunit alpha, 3-[(4-fluorophenyl)methylamino]-5-(4-morpholin-4-ylthieno[3,2-d]pyrimidin-2-yl)phenol, ... (6 entities in total)
• Functional Keywords: pi3k, inhibitor, transferase-inhibitor complex, transferase/inhibitor
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 2
• Total formula weight: 156203.76

Authors

Song, K.,Yang, X.,Zhao, Y.,Jian, Z. (deposition date: 2017-04-13, release date: 2018-04-25, Last modification date: 2024-03-27)

Primary citation

Yang, X.,Zhang, X.,Huang, M.,Song, K.,Li, X.,Huang, M.,Meng, L.,Zhang, J.
New Insights into PI3K Inhibitor Design using X-ray Structures of PI3K alpha Complexed with a Potent Lead Compound.
Sci Rep, 7:14572-14572, 2017

PubMed Abstract: Phosphatidylinositol 3-kinase α is an attractive target to potentially treat a range of cancers. Herein, we described the evolution of a reported PI3K inhibitor into a moderate PI3Kα inhibitor with a low molecular weight. We used X-ray crystallography to describe the accurate binding mode of the compound YXY-4F. A comparison of the p110α-YXY-4F and apo p110α complexes showed that YXY-4F induced additional space by promoting a flexible conformational change in residues Ser773 and Ser774 in the PI3Kα ATP catalytic site. Specifically, residue 773(S) in PI3Kα is quite different from that of PI3Kβ (D), γ (A), and δ (D), which might guide further optimization of substituents around the NH group and phenyl group to improve the selectivity and potency of PI3Kα.

PubMed: 29109464
DOI: 10.1038/s41598-017-15260-5

Experimental method

X-RAY DIFFRACTION (2.97 Å)