X-ray structure of nucleoside diphosphate kinase.
The X-ray structure of a point mutant of nucleoside diphosphate kinase (NDP kinase) from Dictyostelium discoideum has been determined to 2.2 A resolution. The enzyme is a hexamer made of identical subunits with a novel mononucleotide binding fold. Each subunit contains an alpha/beta domain with a four stranded, antiparallel beta-sheet. The topology is different from adenylate kinase, but identical to the allosteric domain of Escherichia coli ATCase regulatory subunits, which bind mononucleotides at an equivalent position. Dimer contacts between NDP kinase subunits within the hexamer are similar to those in ATCase. Trimer contacts involve a large loop of polypeptide chain that bears the site of the Pro----Ser substitution in Killer of prune (K-pn) mutants of the highly homologous Drosophila enzyme. Properties of Drosophila NDP kinase, the product of the awd developmental gene, and of the human enzyme, the product of the nm23 genes in tumorigenesis, are discussed in view of the three-dimensional structure and of possible interactions of NDP kinase with other nucleotide binding proteins.
Dumas
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C
Laboratorie de Biologie Structurale, UMR 9920 CNRS-Université Paris-Sud, Orsay, France.
Lascu
I
I
Moréra
S
S
Glaser
P
P
Fourme
R
R
Wallet
V
V
Lacombe
M L
ML
Véron
M
M
Janin
J
J
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D003461:Crystallography; D004023:Dictyostelium / Q000201:enzymology*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D020559:Monomeric GTP-Binding Proteins; D016296:Mutagenesis; D054778:NM23 Nucleoside Diphosphate Kinases; D009701:Nucleoside-Diphosphate Kinase / Q000737:chemistry*; D011487:Protein Conformation; D011506:Proteins / Q000737:chemistry; D012689:Sequence Homology, Nucleic Acid; D014157:Transcription Factors
D054778:NM23 Nucleoside Diphosphate Kinases; D011506:Proteins; D014157:Transcription Factors; C517938:NME1 protein, human; D009701:Nucleoside-Diphosphate Kinase; D020559:Monomeric GTP-Binding Proteins