X-ray structure of human nucleoside diphosphate kinase B complexed with GDP at 2 A resolution

Background: Nucleoside diphosphate (NDP) kinases provide precursors for DNA and RNA synthesis. In mammals, these enzymes are also involved in cell regulations. Human NDP kinase B, product of the human nm23-H2 gene, is both an enzyme and a transcription factor. It activates transcription of the c-myc oncogene independently of its catalytic function, by binding to its promoter DNA. How do the two functions coexist? Results Recombinant human NDP kinase B was co-crystallized with GDP. The X-ray structure was solved at 2.0 a resolution by molecular replacement from the homologous Drosophila Awd protein. Both enzymes are homo-hexamers with a characteristic β α β β α β fold. GDP binds near the active site His118. The guanine base is in a surface cleft and interacts with the C terminus of another subunit. Conclusion The β α β β α β fold, also present in the ‘palm' domain of Escherichia coli DNA polymerase I and HIV reverse transcriptase, is both a mononucleotide- and a polynucleotide-binding fold. If NDP kinase B binds DNA in the same way as the polymerases, the enzyme must undergo a conformation change in order to carry out gene activation.