Canonical Nucleoside Diphosphate Kinase B Isoform Functions to Regenerate Nucleotide Pools.

A daunting title, perhaps, but an interesting theory. This is the precedent to the work and hopefully the publication we have on NDKB that will be coming out soon.

Nucleoside diphosphate kinase B (NDKB) is a hexameric nucleoside diphosphokinase. Here’s a ribbon model for this hexamer:

It has been suggested that NDKB may play a role in maintaining cytoplasmic GTP pools. This hypothesis is based on the fact that it can catalyze the hydrolysis of the tertiary phosphate on a nucleoside triphosphate and subsequently regenerate another nucleoside triphosphate from a nucleoside diphosphate. Thus, it would be easy for this protein to make GTP from ATP and GDP. In this way, the homeostasis of the nucleotide pools could be maintained by simple stoichiometry. That is to say that nucleotide pools could be maintained, at least in part, by a mechanism wherein a protein such as NDKB has binding affinities that correspond to the general ideal relative concentrations of each nucleotide.

This is a very exciting idea and there has been some work to support this hypothesis, but it remains a hypothesis because the concentration of each nucleotide in vivo is extremely hard to measure. Furthermore, nucleotide pool homeostasis is a very important metabolic factor and so the mechanisms in place to maintain it are likely to be redundant. So, even if there was a reliable way to measure nucleotide pools, they are unlikely to be changed much as a result of NDKB knockdown even if it is functioning in this pathway. Also importantly, NDKB has been shown to be able to function in pathways where its diphosphokinase activity are disposable, such as in COP II assembly and ER export.

There you have it, a peek into NDKB (which, notably, may be called Nm23H2 in mammalian cells). Complete references to the research I’ve alluded to here will be forthcoming.