Open AccessStructure of extracellular signal‐regulated kinase 2 in complex with ATP and ADP
Author(s) -
Zhang Jun,
Shapiro Paul,
Pozharski Edwin
Publication year - 2012
Publication title -
acta crystallographica section f
Language(s) - English
Resource type - Journals
ISSN - 1744-3091
DOI - 10.1107/s1744309112042972
Subject(s) - kinase , mapk/erk pathway , protein kinase a , extracellular , microbiology and biotechnology , biochemistry , cyclin dependent kinase complex , mitogen activated protein kinase kinase , chemistry , binding site , mitogen activated protein kinase , biology
Extracellular signal‐regulated kinases 1 and 2 (ERK1 and ERK2) are members of the mitogen‐activated protein (MAP) kinase family. Constitutive activation of the ERK proteins contributes to the development and progression of numerous human tumors. Thus, ERK1 and ERK2 are promising targets for the design and the development of anticancer drugs. The detailed structural analysis of ERK complexed with ATP can provide valuable information for the design of new ligands that can bind in the ATP‐binding pocket and inhibit ERK activity. In this study, the structures of apo‐form ERK2 and of its complexes with the substrate ATP and the product ADP were determined. Comparison with the structural homolog cyclin‐dependent kinase 2 reveals differences in the way that the ATP binding to the protein is mediated by magnesium. Only minor conformational changes are identified that occur upon substrate binding, and these are limited to the active‐site residues.