THE STRUCTURE OF MITOGEN-ACTIVATED PROTEIN-KINASE P38 AT 2.1-ANGSTROMRESOLUTION

The structure of mitogen-activated protein (MAP) kinase p38 has been s olved at 2.1-Angstrom to an R factor of 21.0%, making p38 the second l ow activity MAP kinase solved to date. Although p38 is topologically s imilar to the MAP kinase ERK2, the phosphorylation Lip (a regulatory l oop near the active site) adopts a different fold in p38, The peptide substrate binding site and the ATP binding site are also different fro m those of ERK2, The results explain why MAP kinases are specific for different activating enzymes, substrates, and inhibitors, A model pres ented for substrate and activator interactions has implications for th e evolution of protein kinase cascades.