title: Structure of extracellular signal-regulated kinase 2 in complex with ATP and ADP.
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.
authors.affiliation: Department of Pharmaceutical Sciences, University of Maryland School of Pharmacy, 20 Penn Street, Baltimore, MD 21201, USA.
authors.forename: Jun
authors.initials: J
authors.lastname: Zhang
authors.forename: Paul
authors.initials: P
authors.lastname: Shapiro
authors.forename: Edwin
authors.initials: E
authors.lastname: Pozharski
mesh_terms: D000244:Adenosine Diphosphate / Q000737:chemistry / Q000378:metabolism*; D000255:Adenosine Triphosphate / Q000737:chemistry / Q000378:metabolism*; D000818:Animals; D001059:Apoproteins / Q000737:chemistry / Q000378:metabolism; D001665:Binding Sites; D018360:Crystallography, X-Ray; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000378:metabolism; D008954:Models, Biological; D011487:Protein Conformation; D051381:Rats
chemical_list: D001059:Apoproteins; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D019950:Mitogen-Activated Protein Kinase 1