1.7 Å STRUCTURE OF THE C-TERMINAL SH2 DOMAIN OF THE P85 SUBUNIT OF HUMAN PHOSPHATIDYLINOSITOL 3-KINASE. Simon Weston, Dean Derbyshire, Alex Breeze & Richard Pauptit, Zeneca Pharmaceuticals, Alderley Park, Macclesfield, UK

The C-terminal SH2 domain of the 85 kDa regulatory subunit of human phosphatidylinositol 3-kinase (an enzyme responsible for a key mitogenic signal invoked by a variety of growth factors) complexed with a specific high-affinity phosphorylated tyrosine pentapeptide sequence from the platelet-derived growth factor receptor has been crystallised in spacegroup C2 and diffracts to 1.7 Å.

All molecular replacement efforts using other SH2 structures as trial models had failed - the structure could only be solved once the NMR structure carried out in our laboratory had produced a sufficiently accurate trial model. This was probably because the crystals were densely packed and the molecular replacement signal suffered from interference from cross-vectors. The structure is currently being refined and will be presented and compared to other SH2 structures.