Three-dimensional structure of nucleoside diphosphate kinase.
Three-dimensional structures are known from X-ray studies of the nucleoside diphosphate (NDP) kinase of many organisms from bacteria to human. All NDP kinases have subunits of about 150 residues with a very similar fold based on the alphabeta sandwich or ferredoxin fold. This fold is found in many nucleotide or polynucleotide-binding proteins with no sequence relationship to NDP kinase. This common fold is augmented here with specific features: a surface alpha-helix hairpin, the Kpn loop, and the C-terminal extension. The alpha-helix hairpin and Kpn loop make up the nucleotide binding site, which is unique to NDP kinase and different from that of other kinases or ATPases. The Kpn loop and the C-terminal extension are also involved in the quaternary structure. Whereas all known eukaryotic NDP kinases, including mitochondral enzymes, are hexamers, some bacterial enzymes are tetramers. However, hexameric and tetrameric NDP kinases are built from the same dimer. The structural environment of the active histidine is identical in all. The nucleotide binding site is also fully conserved, except for a feature implicating C-terminal residues in the hexamer, but not in the tetramer. Structural data on the native and phosphorylated enzyme, complexes with substrates, inhibitor, and a transition state analog, give a solid basis to a mechanism of phosphate transfer in which the largest contributors to catalysis are the 3'-OH of the sugar and the bound Mg2+ in the nucleotide substrate. In contrast, we still lack structural data relating to DNA binding and other functions of NDP kinases.
Janin
J
J
Laboratoire d'Enzymologie et de Biochimie Structurales CNRS UPR9063, Gif-sur-Yvette, France. janin@lebs.cnrs-gif.fr
Dumas
C
C
Moréra
S
S
Xu
Y
Y
Meyer
P
P
Chiadmi
M
M
Cherfils
J
J
D000818:Animals; D001665:Binding Sites; D006801:Humans; D009701:Nucleoside-Diphosphate Kinase / Q000737:chemistry*; D020836:Protein Structure, Quaternary; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary
D009701:Nucleoside-Diphosphate Kinase