Format

Send to

Choose Destination
Acta Crystallogr Sect F Struct Biol Cryst Commun. 2012 Dec 1;68(Pt 12):1434-9. doi: 10.1107/S1744309112042972. Epub 2012 Nov 14.

Structure of extracellular signal-regulated kinase 2 in complex with ATP and ADP.

Author information

1
Department of Pharmaceutical Sciences, University of Maryland School of Pharmacy, 20 Penn Street, Baltimore, MD 21201, USA.

Abstract

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.

PMID:
23192020
PMCID:
PMC3509961
DOI:
10.1107/S1744309112042972
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for International Union of Crystallography Icon for PubMed Central
Loading ...
Support Center