InterPro domain: IPR036850

Nucleoside diphosphate kinases ( 2.7.4.6 ) (NDK) are enzymes required for the synthesis of nucleoside triphosphates (NTP) other than ATP. They provide NTPs for nucleic acid synthesis, CTP for lipid synthesis, UTP for polysaccharide synthesis and GTP for protein elongation, signal transduction and microtubule polymerisation.

NDK are proteins of 17 Kd that act via a ping-pong mechanism in which a histidine residue is phosphorylated, by transfer of the terminal phosphate group from ATP. In the presence of magnesium, the phosphoenzyme can transfer its phosphate group to any NDP, to produce an NTP.

NDK isozymes have been sequenced from prokaryotic and eukaryotic sources. It has also been shown [ 1 ] that the Drosophila awd (abnormal wing discs) protein, is a microtubule-associated NDK. Mammalian NDK is also known as metastasis inhibition factor nm23. The sequence of NDK has been highly conserved through evolution. There is a single histidine residue conserved in all known NDK isozymes, which is involved in the catalytic mechanism [ 2 ].

The enzyme is a hexamer composed by identical subunits with a novel mononucleotide binding fold. Each subunit contains an alpha/beta domain with a four stranded, anti-parallel beta-sheet [ 3 ].

This alpha/beta domain is also found at the C terminus of retinitis pigmentosa 2 protein (XRP2/RP2) [ 4 ]. XRP2, a GTPase-activating protein, is required for maintenance of rod and cone photoreceptor cells in the retina [ 5 ].

1. A Drosophila gene that is homologous to a mammalian gene associated with tumor metastasis codes for a nucleoside diphosphate kinase. Cell 63, 933-40
2. Nucleoside diphosphate kinase from human erythrocytes. Structural characterization of the two polypeptide chains responsible for heterogeneity of the hexameric enzyme. J. Biol. Chem. 266, 8784-9
3. Influences of local and global temperature stimuli on the Lewis-reaction. Pflugers Arch. 367, 291-4
4. Crystal structure of the human retinitis pigmentosa 2 protein and its interaction with Arl3. Structure 14, 367-78
5. Knockout of RP2 decreases GRK1 and rod transducin subunits and leads to photoreceptor degeneration in zebrafish. Hum. Mol. Genet. 24, 4648-59