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)P 4-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)P 4 and surprisingly binds with similar affinity as the natural headgroup. Bz(1,2,3,4)P 4 co-crystallizes with the PKBa PH domain in a fashion also predictable in silico. The 2-phosphate of Bz(1,2,3,4)P 4 does not interact with any residue, and the D5-phosphate of Ins(1,3,4,5)P 4 is not mimicked by Bz(1,2,3,4)P 4. Bz(1,2,3,4)P 4 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.