title: The structure of mitogen-activated protein kinase p38 at 2.1-A resolution.
abstract: The structure of mitogen-activated protein (MAP) kinase p38 has been solved at 2.1-A to an R factor of 21.0%, making p38 the second low activity MAP kinase solved to date. Although p38 is topologically similar to the MAP kinase ERK2, the phosphorylation Lip (a regulatory loop near the active site) adopts a different fold in p38. The peptide substrate binding site and the ATP binding site are also different from those of ERK2. The results explain why MAP kinases are specific for different activating enzymes, substrates, and inhibitors. A model presented for substrate and activator interactions has implications for the evolution of protein kinase cascades.
authors.affiliation: Department of Biochemistry and Biophysics, University of Texas Southwestern Medical Center at Dallas, 75235, USA.
authors.forename: Z
authors.initials: Z
authors.lastname: Wang
authors.forename: P C
authors.initials: PC
authors.lastname: Harkins
authors.forename: R J
authors.initials: RJ
authors.lastname: Ulevitch
authors.forename: J
authors.initials: J
authors.lastname: Han
authors.forename: M H
authors.initials: MH
authors.lastname: Cobb
authors.forename: E J
authors.initials: EJ
authors.lastname: Goldsmith
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000096:biosynthesis / Q000737:chemistry* / Q000302:isolation & purification; D003198:Computer Simulation; D018360:Crystallography, X-Ray; D006801:Humans; D051379:Mice; D019950:Mitogen-Activated Protein Kinase 1; D020928:Mitogen-Activated Protein Kinases; D008958:Models, Molecular; D008961:Models, Structural; D008969:Molecular Sequence Data; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D051381:Rats; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000302:isolation & purification; D017386:Sequence Homology, Amino Acid; D012984:Software; D048051:p38 Mitogen-Activated Protein Kinases
chemical_list: D011994:Recombinant Proteins; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D019950:Mitogen-Activated Protein Kinase 1; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases