Comparative homology modelling of this enzyme inL. donovani suggest that among all of the computationally screened compounds,pentamidine, 1,3-dinitroadamantane,acyclovir and analogs of acyclovir had higher binding affinities than the real substrate (guanosine monophosphate).[3]Thein silico andin-vitro correlation of these compounds were test inLeishmania HGPRT and validates the result.[4]
Mutations in the gene lead tohyperuricemia. 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 ofuric 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 theKelley–Seegmiller syndrome.[6]
Some mutations have been linked togout, 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 atranscription 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'spurine nucleotide resources under hypoxic conditions as found in pathology such asmyocardial ischemia.[8]
Hybridomas are immortal (immune tocellular senescence), HGPRT+ cells that result from fusion of mortal, HGPRT+plasma cells and immortal, HGPRT−myeloma cells. They are created to producemonoclonal antibodies in biotechnology.HAT medium inhibitsde novo synthesis of nucleic acids, killing myeloma cells that cannot switch over to thesalvage pathway, due to lack of HPRT1. The plasma cells in the culture eventually die from senescence, leaving pure hybridoma cells.
^Ansari MY, Dikhit MR, Sahoo GC, Das P (Apr 2012). "Comparative modeling of HGPRT enzyme of L. donovani and binding affinities of different analogs of GMP".International Journal of Biological Macromolecules.50 (3):637–49.doi:10.1016/j.ijbiomac.2012.01.010.PMID22327112.
Sculley DG, Dawson PA, Emmerson BT, Gordon RB (Nov 1992). "A review of the molecular basis of hypoxanthine-guanine phosphoribosyltransferase (HPRT) deficiency".Human Genetics.90 (3):195–207.doi:10.1007/bf00220062.PMID1487231.S2CID25118113.
Ansari MY, Dikhit MR, Sahoo GC, Das P (Apr 2012). "Comparative modeling of HGPRT enzyme of L. donovani and binding affinities of different analogs of GMP".International Journal of Biological Macromolecules.50 (3):637–49.doi:10.1016/j.ijbiomac.2012.01.010.PMID22327112.
Sege-Peterson K, Chambers J, Page T, Jones OW, Nyhan WL (Sep 1992). "Characterization of mutations in phenotypic variants of hypoxanthine phosphoribosyltransferase deficiency".Human Molecular Genetics.1 (6):427–32.doi:10.1093/hmg/1.6.427.PMID1301916.
Lightfoot T, Joshi R, Nuki G, Snyder FF (Mar 1992). "The point mutation of hypoxanthine-guanine phosphoribosyltransferase (HPRTEdinburgh) and detection by allele-specific polymerase chain reaction".Human Genetics.88 (6):695–6.doi:10.1007/BF02265300.PMID1551676.S2CID30114636.
Yamada Y, Goto H, Ogasawara N (1992). "Identification of two independent Japanese mutant HPRT genes using the PCR technique".Purine and Pyrimidine Metabolism in Man VII. Advances in Experimental Medicine and Biology. Vol. 309B. pp. 121–4.doi:10.1007/978-1-4615-7703-4_27.ISBN978-1-4615-7705-8.PMID1840476.
Sculley DG, Dawson PA, Beacham IR, Emmerson BT, Gordon RB (Oct 1991). "Hypoxanthine-guanine phosphoribosyltransferase deficiency: analysis of HPRT mutations by direct sequencing and allele-specific amplification".Human Genetics.87 (6):688–92.doi:10.1007/BF00201727.PMID1937471.S2CID2197550.
Gordon RB, Sculley DG, Dawson PA, Beacham IR, Emmerson BT (1991). "Identification of a single nucleotide substitution in the coding sequence of in vitro amplified cDNA from a patient with partial HPRT deficiency (HPRTBRISBANE)".Journal of Inherited Metabolic Disease.13 (5):692–700.doi:10.1007/BF01799570.PMID2246854.S2CID34183501.
Edwards A, Voss H, Rice P, Civitello A, Stegemann J, Schwager C, Zimmermann J, Erfle H, Caskey CT, Ansorge W (Apr 1990). "Automated DNA sequencing of the human HPRT locus".Genomics.6 (4):593–608.doi:10.1016/0888-7543(90)90493-E.PMID2341149.
Gibbs RA, Nguyen PN, Edwards A, Civitello AB, Caskey CT (Jun 1990). "Multiplex DNA deletion detection and exon sequencing of the hypoxanthine phosphoribosyltransferase gene in Lesch-Nyhan families".Genomics.7 (2):235–44.doi:10.1016/0888-7543(90)90545-6.PMID2347587.
Skopek TR, Recio L, Simpson D, Dallaire L, Melancon SB, Ogier H, O'Neill JP, Falta MT, Nicklas JA, Albertini RJ (Jun 1990). "Molecular analyses of a Lesch-Nyhan syndrome mutation (hprtMontreal) by use of T-lymphocyte cultures".Human Genetics.85 (1):111–6.doi:10.1007/BF00276334.PMID2358296.S2CID21412991.
