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

Z. Wang, P. C. Harkins, R. J. Ulevitch, J. Han, M. H. Cobb, E. J. Goldsmith

Research output: Contribution to journalArticle

234 Scopus citations

Abstract

The structure of mitogen-activated protein (MAP) kinase p38 has been solved at 2.1-Å 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.

Original languageEnglish (US)
Pages (from-to)2327-2332
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume94
Issue number6
DOIs
Publication statusPublished - 1997

    Fingerprint

ASJC Scopus subject areas

  • Genetics
  • General

Cite this