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PROSITE documentation PDOC00409 [for PROSITE entry PS00469]

Nucleoside diphosphate kinases active site





Description

Nucleoside diphosphate kinases (EC 2.7.4.6) (NDK) [1] 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 polymerization.

In eukaryotes, there seems to be a small family of NDK isozymes each of which acts in a different subcellular compartment and/or has a distinct biological function. Eukaryotic NDK isozymes are hexamers of two highly related chains (A and B) [2]. By random association (A6, A5B...AB5, B6), these two kinds of chain form isoenzymes differing in their isoelectric point.

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 [3] 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]. Our signature pattern contains this residue.

Last update:

May 2004 / Text revised.

Technical section

PROSITE method (with tools and information) covered by this documentation:

NDP_KINASES, PS00469; Nucleoside diphosphate kinases active site  (PATTERN)


References

1AuthorsParks R., Agarwal R.
Source(In) The Enzymes (3rd edition) 8:307-334(1973).

2AuthorsGilles A.-M., Presecan E., Vonica A., Lascu I.
TitleNucleoside diphosphate kinase from human erythrocytes. Structural characterization of the two polypeptide chains responsible for heterogeneity of the hexameric enzyme.
SourceJ. Biol. Chem. 266:8784-8789(1991).
PubMed ID1851158

3AuthorsBiggs J., Hersperger E., Steeg P.S., Liotta L.A., Shearn A.
TitleA Drosophila gene that is homologous to a mammalian gene associated with tumor metastasis codes for a nucleoside diphosphate kinase.
SourceCell 63:933-940(1990).
PubMed ID2175255



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