9HHM

Crystal structure of phosphatidyl inositol 4-kinase II beta in complex with HH5129

This is a non-PDB format compatible entry.

Summary for 9HHM

• Entry DOI: 10.2210/pdb9hhm/pdb
• Descriptor: Phosphatidylinositol 4-kinase type 2-beta,Endolysin, (1~{S},2~{S},4~{S},5~{R})-6-[[[[(2~{R},3~{S},4~{R},5~{R})-5-(6-aminopurin-9-yl)-3,4-bis(oxidanyl)oxolan-2-yl]methoxy-bis(oxidanylidene)-$l^{6}-phosphanyl]oxy-bis(oxidanylidene)-$l^{6}-phosphanyl]methyl-bis(oxidanylidene)-$l^{6}-phosphanyl]oxycyclohexane-1,2,3,4,5-pentol (3 entities in total)
• Functional Keywords: lipid, kinase, inhibitor, pi4k2b, pi4p, transferase
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 2
• Total formula weight: 120555.03

Authors

Klima, M.,Boura, E. (deposition date: 2024-11-22, release date: 2025-12-03, Last modification date: 2026-05-20)

Primary citation

Hrebabecky, H.,Klima, M.,Dejmek, M.,Krupa, P.,Fernandez, M.R.,Davidova, E.,Benysek, J.,Martinez-Seara, H.,Rozycki, B.,Boura, E.,Nencka, R.
Compounds mimicking the Michaelis-Menten transition state of the phosphatidylinositol 4-kinase.
Bioorg.Med.Chem., 139:118666-118666, 2026

PubMed Abstract: Phosphatidylinositol 4-kinases (PI4Ks) are crucial enzymes in lipid signaling responsible for generating phosphatidylinositol-4-phosphate (PI4P). Although the ATP-binding site of PI4Ks has been extensively studied, the structural characterization of their natural substrate, phosphatidylinositol (PI), bound to the enzyme remains elusive. In this study, we synthesized novel non-hydrolyzable Michaelis-Menten transition state mimetics in which the ADP molecule is covalently linked to inositol-4-phosphate or simple phosphatidylinositol-4-phosphate via a methylene or ethylene bridge. During our synthesis efforts, we successfully addressed the significantly limited reactivity at position 4 of inositols by utilizing P(III) phosphorus reagents, which proved crucial for the synthesis of these mimetics. For the simplest ADP-C-4PI analogue, we obtained a crystal structure of PI4K2B, which can be used to understand how these phospholipids are phosphorylated on membrane surfaces.

PubMed: 42086018
DOI: 10.1016/j.bmc.2026.118666

Experimental method

X-RAY DIFFRACTION (2.25 Å)