Work

The structure of mitogen-activated protein kinase p38 at 2.1-Å resolution

Year: 1997

Type: article

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.

Source: Proceedings of the National Academy of Sciences

DOI: 10.1073/pnas.94.6.2327

Authors: Zhulun Wang, Paul C. Harkins, Richard J. Ulevitch, Jiahuai Han, Melanie H. Cobb, Elizabeth J. Goldsmith

Institutions: Scripps Research Institute, The University of Texas Southwestern Medical Center

Language: English

Topic: Protein Kinase Regulation and GTPase Signaling

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

Open Access status: green

Funders: University of Texas Southwestern Medical Center, National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases

Awards: G5571578046, Interactions and Dual Phosphorylation in MAP Kinase Cascades