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X-ray structure of nucleoside diphosphate kinase
1Laboratorie de Biologie Structurale, UMR 9920 CNRS-Université Paris-Sud, Orsay, France.
The EMBO Journal
|September 1, 1992
Summary
The crystal structure of Dictyostelium discoideum nucleoside diphosphate kinase (NDP kinase) reveals a novel mononucleotide binding fold. This structure provides insights into NDP kinase function and interactions relevant to tumorigenesis.
Area of Science:
- Biochemistry
- Structural Biology
- Enzymology
Background:
- Nucleoside diphosphate kinase (NDP kinase) is crucial for cellular nucleotide pools.
- NDP kinase is implicated in tumorigenesis via the human nm23 genes.
- Understanding NDP kinase structure is key to its biological roles.
Purpose of the Study:
- To determine the X-ray structure of a point mutant of Dictyostelium discoideum NDP kinase.
- To elucidate the novel mononucleotide binding fold and subunit interactions.
- To relate structural findings to NDP kinase function in development and disease.
Main Methods:
- X-ray crystallography
- Protein structure determination to 2.2 A resolution
- Comparative structural analysis
Main Results:
- The hexameric NDP kinase exhibits a novel alpha/beta domain with a four-stranded antiparallel beta-sheet.
- The mononucleotide binding fold topology differs from adenylate kinase but matches Escherichia coli ATCase regulatory subunits.
- Dimer and trimer contacts reveal similarities to ATCase and highlight a mutation site in Drosophila NDP kinase.
Conclusions:
- The determined structure provides a detailed view of the NDP kinase active site and oligomeric assembly.
- Structural similarities suggest conserved mechanisms for mononucleotide binding across different species.
- The findings offer a structural basis for understanding NDP kinase roles in development (Drosophila awd gene) and tumorigenesis (human nm23 genes).