2UVM

Structure of PKBalpha PH domain in complex with a novel inositol headgroup surrogate, benzene 1,2,3,4-tetrakisphosphate

Summary for 2UVM

• Entry DOI: 10.2210/pdb2uvm/pdb
• Related: 1H10 1UNP 1UNQ 1UNR
• Descriptor: RAC-ALPHA SERINE/THREONINE-PROTEIN KINASE, BENZENE-1,2,3,4-TETRAYL TETRAKIS[DIHYDROGEN (PHOSPHATE)], SODIUM ION, ... (4 entities in total)
• Functional Keywords: transferase, glycogen biosynthesis, translation regulation, serine/threonine-protein kinase, phosphoinositide, protein kinase b, glucose metabolism, nuclear protein, cell signalling, phosphorylation, nucleotide-binding, glycogen metabolism, kinase, cancer, inositol, apoptosis, transport, carbohydrate metabolism, ph domain, atp-binding, sugar transport
• Biological source: HOMO SAPIENS (HUMAN)
• Cellular location: Cytoplasm: P31749
• Total number of polymer chains: 1
• Total formula weight: 15171.61

Authors

Komander, D.,Mills, S.J.,Trusselle, M.N.,Safrany, S.T.,van Aalten, D.M.F.,Potter, B.V.L. (deposition date: 2007-03-12, release date: 2007-04-17, Last modification date: 2023-12-13)

Primary citation

Mills, S.J.,Komander, D.,Trusselle, M.N.,Safrany, S.T.,Van Aalten, D.M.F.,Potter, B.V.L.
Novel Inositol Phospholipid Headgroup Surrogate Crystallised in the Pleckstrin Homology Domain of Protein Kinase Balpha.
Acs Chem.Biol., 2:242-, 2007

PubMed Abstract: Protein kinase B (PKB/Akt) plays a key role in cell signaling. The PH domain of PKB binds phosphatidylinositol 3,4,5-trisphosphate translocating PKB to the plasma membrane for activation by 3-phosphoinositide-dependent protein kinase 1. The crystal structure of the headgroup inositol 1,3,4,5-tetrakisphosphate Ins(1,3,4,5)P4-PKB complex facilitates in silico ligand design. The novel achiral analogue benzene 1,2,3,4-tetrakisphosphate (Bz(1,2,3,4)P4) possesses phosphate regiochemistry different from that of Ins(1,3,4,5)P4 and surprisingly binds with similar affinity as the natural headgroup. Bz(1,2,3,4)P4 co-crystallizes with the PKBalpha PH domain in a fashion also predictable in silico. The 2-phosphate of Bz(1,2,3,4)P4 does not interact with any residue, and the D5-phosphate of Ins(1,3,4,5)P4 is not mimicked by Bz(1,2,3,4)P4. Bz(1,2,3,4)P4 is an example of a simple inositol phosphate surrogate crystallized in a protein, and this approach could be applied to design modulators of inositol polyphosphate binding proteins.

PubMed: 17432822
DOI: 10.1021/CB700019R

Experimental method

X-RAY DIFFRACTION (1.94 Å)