Disease relevance of hpt

• The hpt gene from the archaeon Methanobacterium thermoautotrophicum, encoding hypoxanthine (guanine) phosphoribosyltransferase, was cloned by functional complementation into Escherichia coli [1].
• Isolation of purine auxotrophic mutants of Lactococcus lactis and characterization of the gene hpt encoding hypoxanthine guanine phosphoribosyltransferase [2].
• The hypoxanthine phosphoribosyltransferase (HPRT) from Trypanosoma cruzi, etiologic agent of Chagas' disease, was cocrystallized with the inosine analogue Formycin B (FmB) and the structure determined to 1.4 A resolution [3].

High impact information on hpt

• Further L. monocytogenes with deletion in its PrfA-regulated hpt gene was found to be impaired in replication when injected into the cytosol [4].
• Complementation of the hpt mutation with a plasmid carrying the wild-type hpt gene restored the replication ability in the cytosol [4].
• Site-specific rates of excision repair of benzo[a]pyrene diol epoxide adducts in the hypoxanthine phosphoribosyltransferase gene of human fibroblasts: correlation with mutation spectra [5].
• Hypoxanthine phosphoribosyltransferase and guanine phosphoribosyltransferase activities are essential for the supply of guanine nucleotides in Schistosoma mansoni schistosomules [6].
• A single amino acid substitution in the human and a bacterial hypoxanthine phosphoribosyltransferase modulates specificity for the binding of guanine [7].

Chemical compound and disease context of hpt

• Of the known 6-oxopurine phosphoribosyltransferase (PRTase) structures, E. coli HPRT is most similar in structure to that of Tritrichomonas foetus HGXPRT, with a rmsd for 150 Calpha atoms of 1.0 A [8].
• E. coli HPRT is unique among the known 6-oxopurine PRTases in that it exhibits a marked preference for hypoxanthine as substrate over both xanthine and guanine [8].

Biological context of hpt

• The hpt-encoded amino acid sequence is most similar to adenine phosphoribosyltransferases, but the encoded enzyme has activity only with hypoxanthine and guanine [1].
• The nucleotide sequence of this hpt gene was determined [2].
• It was, however found that in addition to these two loci the molecular cloning of another gene, which has been identified as hpt, in pBR322 confers a Gua+ phenotype on NT31 [9].
• A gene, encoding a protein homologous to an essential Escherichia coli protein, FtsH, was identified adjacent to the hpt gene and the trnA operon in the Gram-positive bacterium Lactococcus lactis [10].
• We have cloned the gene encoding the G. lamblia GPRTase by complementation of the E. coli strain Sø609 (delta gpt-pro-lac, thi, hpt, pup, purH,J, strA) with a genomic library consisting of Sau3AI-digested G. lamblia DNA inserted into the Bluescript vector [11].

Associations of hpt with chemical compounds

• The synthesis of the recombinant enzyme is apparently limited by the presence of the rare arginine codons AGA and AGG and the rare isoleucine AUA codon on the hpt gene [1].
• Other reports have shown that this expression system can generate relatively modest levels of active hypoxanthine/guanine phosphoribosyltransferase (HPRT; hypoxanthine phosphoribosyltransferase; IMP:pyrophosphate phosphoribosyltransferase, EC 2.4.2.8), which carries part of the signal peptide but remains in the cytosol of the bacteria [12].
• Mutants with lesions in the hpt gene, encoding hypoxanthine phosphoribosyltransferase, were shown to be >35-fold more resistant to the toxic base analog 8-aza-2,6-diaminopurine (8ADP) than was the wild type [13].
• Streptozotocin and the haloethyl nitrosoureas, chlorozotocin and bis-chloroethylnitrosourea were less efficient in inducing HPRT-deficient mutants and a smaller degree of protection was afforded by the transfected genes [14].
• Significant protection against the mutagenic effects of N-methyl-N-nitrosourea and ethylmethanesulphonate at the hypoxanthine phosphoribosyltransferase (HPRT) locus was observed in clone 8 and SB cells [14].

Analytical, diagnostic and therapeutic context of hpt

• To test whether the increase in the relative frequency of mutations resulted from inefficient repair at these sites, we adapted ligation-mediated PCR to measure the rates of removal of BPDE adducts from individual sites in exon 3 of the HPRT gene [5].

References