2UVM: Structure Of Pkbalpha Ph Domain In Complex With A Novel Inositol Headgroup Surrogate, Benzene 1,2,3,4- Tetrakisphosphate

Citation:
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.
PDB ID: 2UVMDownload
MMDB ID: 45763
PDB Deposition Date: 2007/3/12
Updated in MMDB: 2012/12
Experimental Method:
x-ray diffraction
Resolution: 1.94  Å
Source Organism:
Similar Structures:
Biological Unit for 2UVM: monomeric; determined by author and by software (PQS)
Molecular Components in 2UVM
Label Count Molecule
Protein (1 molecule)
1
Rac-alpha Serine/threonine-protein Kinase(Gene symbol: AKT1)
Molecule annotation
Chemicals (2 molecules)
1
1
2
1
* Click molecule labels to explore molecular sequence information.

Citing MMDB
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