Pim1 + AMPPNP

Pim1 + AMPPNP

Pim1 + AMPPNP: Human Proviral Integration Site for MuLV in complex with AMPPNP and consensus peptide
PDB Code: 2BZK
Description
Pim1 phosphorylates targets such as 4E-BP1 and BAD that promote pro-survival cytokine signalling and contributes to the development of tumours of the hematopoetic and lymphoid systems. In collaboration with Dr Ben Turk (Yale University) we have recently determined the substrate specificity for all three Pim-family kinases and solved the crystal structure of Pim1 bound to a high affinity peptide substrate in complexes with either the ATP analog AMP- PNP (PDB 2BZK) or the inhibitor BIM-1 (PDB 2BIL).
The AMP-PNP complex structure was solved to 2.45 Å resolution with density defining 7 residues (shown in bold) from the bound peptide ARKRRRHPSGPPTA. Basic residues upstream of the phosphorylation site have an unanticipated mode of recognition, distinct from that of other kinases with similar substrate specificity. The Pim1 hinge region lacks a hydrogen bond acceptor due to its +3 Pro residue, but binds AMP-PNP in an otherwise canonical fashion. In our structure the ?-phosphate points away from the substrate serine and towards the glycine-rich loop which is disordered.

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