Hypoxanthine guanine phosphoribosyl transferase
| Hypoxanthine guanine phosphoribosyl transferase | ||
|---|---|---|
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| Tetramer representation according to PDB 1BZY | ||
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Existing structural data: 1bzy, 1d6n, 1hmp, 1z7g |
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| Properties of human protein | ||
| Mass / length primary structure | 217 aa; 24.4 kDa | |
| Secondary to quaternary structure | Homotetramer | |
| Cofactor | 2 mg 2+ | |
| Identifier | ||
| Gene names | HPRT1 ; HGPRT; HPRT | |
| External IDs | ||
| Enzyme classification | ||
| EC, category | 2.4.2.8 , glycosyl transferase | |
| Response type | Phosphoribosylation | |
| Substrate | Hypoxanthine (guanine) + 5-phospho-alpha-D-ribose 1-diphosphate | |
| Products | IMP (GMP) + diphosphate | |
| Occurrence | ||
| Parent taxon | Creature | |
| Orthologue | ||
| human | mouse | |
| Entrez | 3251 | 15452 |
| Ensemble | ENSG00000165704 | ENSMUSG00000025630 |
| UniProt | P00492 | Q6TDG6 |
| Refseq (mRNA) | NM_000194 | NM_013556 |
| Refseq (protein) | NP_000185 | NP_038584 |
| Gene locus | Chr X: 133.42 - 133.46 Mb | Chr X: 49.23 - 49.27 Mb |
| PubMed search | 3251 |
15452
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The hypoxanthine-guanine phosphoribosyl transferase (HGPRT) or hypoxanthine phosphoribosyl transferase 1 (HPRT1) is an enzyme in purine metabolism of eukaryotes . In humans, changes in HPRT1 through gene mutations can lead to metabolic diseases such as Lesch-Nyhan syndrome and Kelley-Seegmiller syndrome . The function of the enzyme is very sensitive to changes in the gene, which is why the gene in a cell line is used as a target for a mutation test.
synthesis
The HPRT1 gene consists of 10 exons , which are distributed over a 40 kilobase long section on the X chromosome . After translation and removal of the first methionine , a protein of 217 amino acids and 24 kDa remains. Four of these molecules bind with two magnesium ions each (one of them only loosely) as cofactors to the functional HPRT1 enzyme, which is located in the cytoplasm .
Catalyzed reaction
The purine bases adenine , hypoxanthine , xanthine and guanine can be recycled with the help of two enzymes (HPRT1 and APRT ) by being reconstructed to a nucleotide with a phosphoribosyl residue . This is very sensible, because firstly, ATP can be saved (the formation of a purine costs at least 7 ( AMP ) or 9 ( GMP ) high-energy phosphate bonds) and secondly, uric acid formation is drastically reduced (so-called salvage pathway )
pathology
A large number of changes in the HPRT1 gene are known, so-called repeats (repetitions of a base) being rare. Mainly it concerns insertions , deletions and point mutations in the gene. Half of the modified gene products are sized, the rest are changes to an amino acid.
The function of HPRT1 is sensitive to changes in the amino acid sequence. Slight impairments of function cause symptoms similar to gout and are known as Kelley-Seegmiller syndrome. All severe metabolic diseases are grouped under the Lesch-Nyhan syndrome .
Mutation test
In the HPRT1 gene mutation test , possible mutants are recognized by the loss of the enzyme's activity . The hamster lung cell line (V79 cells, ATCC No. CCL-93) is usually used for the test.
The selection of the mutants is based on the different degrees of toxicity of the synthetic purine base 6-thioguanine (TG) for the mutated and unchanged cells . In cells with functional HPRT1, TG is converted into nucleotides that are so toxic that they die. The loss of HPRT activity due to mutagenic substances, on the other hand, leads to resistance to TG and thus to the survival and accumulation of cells with mutated HPRT1. This can be quantified microscopically.
Individual evidence
- ↑ Ensembl entry
- ↑ UniProt entry
- ↑ s. Wikibooks link
- ↑ Hypoxanthine guanine phosphoribosyl transferase. In: Online Mendelian Inheritance in Man . (English).
Web links
- reactome: guanine + PRPP ⇒ GMP + PPi
- reactome: Hypoxanthine + PRPP ⇒ IMP + PPi