title: Adenosine 5'-diphosphate binding and the active site of nucleoside diphosphate kinase.
abstract: The X-ray structure of nucleoside diphosphate kinase (NDP kinase) from the slime mold Dictyostelium discoideum has been determined to 2.2-A resolution and refined to an R-factor of 0.19 with and without bound ADP-Mg2+. The nucleotide binds near His 122, a residue which becomes phosphorylated during the catalytic cycle. The mode of binding is different from that observed in other phosphokinases, and it involves no glycine-rich sequence. The adenine base makes only nonpolar contacts with the protein. It points outside, explaining the lack of specificity of NDP kinase toward the base. The ribose 2'- and 3'-hydroxyls and the pyrophosphate moiety are H-bonded to polar side chains. A Mg2+ ion bridges the alpha- to the beta-phosphate which approaches the imidazole group of His 122 from the N delta side. The geometry at the active site in the ADP-Mg2+ complex suggests a mechanism for catalysis whereby the gamma-phosphate of a nucleoside triphosphate can be transferred onto His 122 with a minimum of atomic motion.
authors.affiliation: Laboratoire de Biologie Structurale, UMR 9920 CNRS-Université Paris-Sud, Gif-sur-Yvette, France.
authors.forename: S
authors.initials: S
authors.lastname: Moréra
authors.forename: I
authors.initials: I
authors.lastname: Lascu
authors.forename: C
authors.initials: C
authors.lastname: Dumas
authors.forename: G
authors.initials: G
authors.lastname: LeBras
authors.forename: P
authors.initials: P
authors.lastname: Briozzo
authors.forename: M
authors.initials: M
authors.lastname: Véron
authors.forename: J
authors.initials: J
authors.lastname: Janin
mesh_terms: D000244:Adenosine Diphosphate / Q000378:metabolism*; D000818:Animals; D001665:Binding Sites; D003460:Crystallization; D018360:Crystallography, X-Ray; D004023:Dictyostelium / Q000201:enzymology; D004926:Escherichia coli / Q000201:enzymology; D006639:Histidine / Q000378:metabolism; D046911:Macromolecular Substances; D008274:Magnesium / Q000378:metabolism; D008958:Models, Molecular; D015394:Molecular Structure; D009701:Nucleoside-Diphosphate Kinase / Q000737:chemistry* / Q000378:metabolism*; D010766:Phosphorylation; D017433:Protein Structure, Secondary; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism
chemical_list: D046911:Macromolecular Substances; D011994:Recombinant Proteins; D006639:Histidine; D000244:Adenosine Diphosphate; D009701:Nucleoside-Diphosphate Kinase; D008274:Magnesium