4L1B: Crystal Structure of p110alpha complexed with niSH2 of p85alpha

Citation:
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 PI3Kalpha-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 PI3Kalpha-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 PI3Kalpha inhibitors.
PDB ID: 4L1BDownload
MMDB ID: 116376
PDB Deposition Date: 2013/6/3
Updated in MMDB: 2017/11
Experimental Method:
x-ray diffraction
Resolution: 2.586  Å
Source Organism:
Similar Structures:
Biological Unit for 4L1B: dimeric; determined by author and by software (PISA)
Molecular Components in 4L1B
Label Count Molecule
Proteins (2 molecules)
1
Phosphatidylinositol 4,5-bisphosphate 3-kinase Catalytic Subunit Alpha Isoform(Gene symbol: PIK3CA)
Molecule annotation
1
Phosphatidylinositol 3-kinase Regulatory Subunit Alpha(Gene symbol: PIK3R1)
Molecule annotation
Chemical (1 molecule)
1
1
* Click molecule labels to explore molecular sequence information.

Citing MMDB
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