PDBsum entry 2uvm

Transferase

PDB id: 2uvm

Contents

Protein chain

116 a.a.

Ligands

GVF

Metals

_NA

Waters ×53

References listed in PDB file

Key reference

• Title: Novel inositol phospholipid headgroup surrogate crystallized in the pleckstrin homology domain of protein kinase balpha.
• Authors: S.J.Mills, D.Komander, M.N.Trusselle, S.T.Safrany, D.M.Van aalten, B.V.Potter.
• Ref.: Acs Chem Biol, 2007, 2, 242-246. [DOI no: 10.1021/cb700019r]
• PubMed id: 17432822

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.