Comparative homology modelling of this enzyme in L. donovani suggest that among all of the computationally screened compounds,
pentamidine, 1,3-dinitro
adamantane,
acyclovir and analogs of acyclovir had higher binding affinities than the real substrate (guanosine monophosphate).[3]
The
in silico and
in-vitro correlation of these compounds were test in
Leishmania HGPRT and validates the result.[4]
Role in disease
Mutations in the gene lead to
hyperuricemia. At least 67 disease-causing mutations in this gene have been discovered:[5]
Some men have partial (up to 20% less activity of the enzyme) HGPRT deficiency that causes high levels of
uric acid in the blood, which leads to the development of gouty arthritis and the formation of uric acid stones in the urinary tract. This condition has been named the
Kelley–Seegmiller syndrome.[6]
Some mutations have been linked to
gout, the risk of which is increased in hypoxanthine-guanine phosphoribosyltransferase deficiency.
HPRT expression on the mRNA and protein level is induced by hypoxia inducible factor 1 (
HIF1A). HIF-1 is a
transcription factor that directs an array of cellular responses that are used for adaptation during oxygen deprivation. This finding implies that HPRT is a critical pathway that helps preserve the cell's
purine nucleotide resources under hypoxic conditions as found in pathology such as
myocardial ischemia.[8]
Creation of hybridomas
Hybridomas are immortal (immune to
cellular senescence), HGPRT+ cells that result from fusion of mortal, HGPRT+plasma cells and immortal, HGPRT−myeloma cells. They are created to produce
monoclonal antibodies in biotechnology.
HAT medium inhibits
de novo synthesis of nucleic acids, killing myeloma cells that cannot switch over to the
salvage pathway, due to lack of HPRT1. The plasma cells in the culture eventually die from senescence, leaving pure hybridoma cells.
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