Nucleoside-diphosphate kinase
The general reaction via ping-pong mechanism is as follows: XDP + YTP ←→ XTP + YDP (X and Y each represent different nitrogenous base).
[1] Other activities include cell proliferation, differentiation and development, signal transduction, G protein-coupled receptor, endocytosis, and gene expression.
NDPK are homohexameric proteins made up of monomers approximately 152 amino acids long with a theoretical weight of 17.17KDa.
NDPK are found in all cells, displaying not much specificity towards the types of nucleoside bases and are capable of accepting nucleotides and deoxyribonucleotides as substrates or donors.
[4] NDPK utilize specific enzyme kinetics for multi-substrate reaction, namely ping-pong mechanism.
A ping-pong mechanism integrates phosphorylation of a histidine residue by transferring terminal phosphate group (γ-phosphate) from ATP to NDP β-phosphate in order to produce a NTP, and NDPK catalyzes such reversible reactions.
NDPK controls K+ channels, G proteins, cell secretion, cellular energy production, and UTP synthesis.
However, consumption of ATP would definitely influence the cellular energy balance, which brings upon the regulation of AMP-activated protein kinase (AMPK).
NDPK function has been studied in Escherichia coli, Bacillus subtilis, Salmonella typhimurium, Micrococcus luteus, and Myxococcus xanthus.
[10] However, in most prokaryotes, NDPK expression levels are involved in the cell growth, development and differentiation of the organism, especially bacteria.
(p)ppGpp biosynthesis is a part of the purine metabolism pathway and coordinates a series of cellular activities in response to nutritional abundances.
Highly conserved homologues of the Nm23 gene have been found in prokaryotes, more specifically, Myxococcus xanthus, a gram-negative soil bacteria.
Furthermore, NDPK is involved with the signal transduction processes and G protein-coupled receptor endocytosis as it transfers a phosphate group onto the G β-subunits and convert GDP to GTP.
[15] In addition to signaling, NDPK is involved in controlling K+ channels, cell secretion, and cellular energy production.
[16] Type II NDPK is concentrated in the chloroplast and it is believed to be involved in the photosynthesis process and the oxidative stress management, but its function is not yet known clearly.
However, other tumor types such as ovarian cancers, neuroblastoma and hematological malignancies displayed upregulated NM23 levels in patient samples.
Invasion of cancer occurs due to changes in cell adhesion and it is caused by gene expression changes in the epithelial-mesenchymal transition (EMT).
Surprisingly, there are many adhesion molecules, motility factors, signaling pathways, proteolytic events, EMT hallmarks, and other transcriptional programs that have been linked to the Nme1 proteins.
