2X6I: THE CRYSTAL STRUCTURE OF THE DROSOPHILA CLASS III PI3-KINASE VPS34 IN COMPLEX WITH PIK-90

Citation:
Abstract
Phosphoinositide 3-kinases (PI3Ks) are lipid kinases with diverse roles in health and disease. The primordial PI3K, Vps34, is present in all eukaryotes and has essential roles in autophagy, membrane trafficking, and cell signaling. We solved the crystal structure of Vps34 at 2.9 angstrom resolution, which revealed a constricted adenine-binding pocket, suggesting the reason that specific inhibitors of this class of PI3K have proven elusive. Both the phosphoinositide-binding loop and the carboxyl-terminal helix of Vps34 mediate catalysis on membranes and suppress futile adenosine triphosphatase cycles. Vps34 appears to alternate between a closed cytosolic form and an open form on the membrane. Structures of Vps34 complexes with a series of inhibitors reveal the reason that an autophagy inhibitor preferentially inhibits Vps34 and underpin the development of new potent and specific Vps34 inhibitors.
PDB ID: 2X6IDownload
MMDB ID: 81192
PDB Deposition Date: 2010/2/17
Updated in MMDB: 2011/05
Experimental Method:
x-ray diffraction
Resolution: 3.4  Å
Source Organism:
Similar Structures:
Biological Unit for 2X6I: dimeric; determined by author and by software (PISA)
Molecular Components in 2X6I
Label Count Molecule
Proteins (2 molecules)
2
Phosphotidylinositol 3 Kinase 59F
Molecule annotation
Chemicals (2 molecules)
1
2
* Click molecule labels to explore molecular sequence information.

Citing MMDB
.