Function
Phosphatidylinositol 4-kinase (PI4K) modulates inter-organelle lipid tarfficking. phosphoinositide signalling and intracellular vescicle trafficking. The catalytic domain of PI4K is required for the synthesis of phosphatidylinositol 4-phosphate[1]. The mammalian PI4K are classified into 2 types - II and III - based on their molecular mass and modulation by detergent and adenosine.
- Phosphatidylinositol 4-kinase IIα accounts for the bulk of PI4K activity in the brain and is concentrated at synapses[2].
- Phosphatidylinositol 4-kinase IIβ synthesises phosphatidylinositok 4,5-bisphosphate at the plasma membrane[3].
- Phosphatidylinositol 4-kinase IIIα catalyses the synthesis of phosphatidylinositol 4-phosphate in hepatitis C virus cells[4].
- Phosphatidylinositol 4-kinase IIIβ is a key enzyme in the control of spingomyelin synthesis by controlling the flow of ceramide from the endoplasmic reticulum to the Golgi compartment[5].
Relevance
Phosphatidylinositol 4-kinase IIIβ is required for cellular entry by pseudoviruses bearing the SARS-CoV spike protein. Inhibitors of hPI4KIIIβ blocked the entry of SARS pseudoviruses into cells[6].
Structural highlights
The 3D structure of phosphatidylinositol 4-kinase IIIβ complex with an inhibitor shows the making various [7]. Based on superposition of this structure on others with PI4K bound to ATP it is evident that the inhibitor's 5-member ring overlap the adenine ring of ATP suggesting that this inhibitor functions by sterically blocking the binding of ATP to the enzyme.
