Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.4.2.8 (hypoxanthine-guanine phosphoribosyltransferase)
 2,527 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hypoxanthine phosphoribosyltransferase (EC 2.4.2.8) from rat brain or human erytherocytes can be irreversibly inactivated by incubation with periodate-oxidized analogues of the enzyme products GMP or IMP. This inhibition is specific and directed against the product binding site of the enzyme. Inactivation is not produced by periodate-oxidized AMP or other aldehydes, for example periodate-oxidized glycerol. The inactivation is concomitant with the binding of the inhibitor to the enzyme protein. The bound inhibitor cannot be removed from the protein by dialysis, Sephadex chromatography or polyacrylamide-gel electrophoresis. Adenine phosphoribosyltransferase (EC 2.4.2.7), on the other hand, is not influenced by any of the inhibitors mentioned above.
 ...
PMID:Irreversible inactivation of hypoxanthine phosphoribosyltransferase by periodate oxidized nucleotides. 16 42

Clonal lines, with either partial or total deficiency of adenine phosphoribosyltransferase (APRT) were derived from the WI-L2 long-term human lymphocyte line by selection for resistance to the adenine analogs 8-azaadenine or 2,6-diaminopurine. Resistance to 8-azaadenine also conferred resistance to 2,6 diaminopurine and vice versa. Cells with 30--40% of wild-type APRT activity were selected by resistance to 0.01 mM 2,6-diaminopurine or 1.40 mM 8-azaadenine. The APRT in the 8-azaadinine-resistant cells exhibited a four- to sevenfold increase in the apparent Km for adenine. Activities of three other purine reutilization and interconversion enzymes in the resistant cells, including hypoxanthine phosphoribosyltransferase (HPRT), adenosine kinase, and adenosine deaminase, were within the range of wild-type activities. The doubling times of the APRT-deficient cells in purine-free medium was not different from wild-type cells. The APRT in the 8-azaadenine-resistant cells did not have an altered mobility in glycerol gradients as compared to wild-type cells. The rate of purine synthesis de novo and intracellular levels of 5-phosphoribosyl-1-pyrophosphate were unchanged in the APRT-deficient cells as compared to WI-L2. The ability of the cells to reutilize exogenous adenine, however, was severely impaired.
 ...
PMID:Purine reutilization and synthesis de novo in long-term human lymphocyte cell lines deficient in adenine phosphoribosyltransferase activity. 69 20

A method for reducing the degree of heterogeneity in the electrophoretic enzyme activity pattern of hypoxanthine phosphoribosyltransferase preparations by incubation with a (magnesium) phosphoribosyl diphosphate substrate is described. Hypoxanthine phosphoribosyltransferase was isolated from human erythrocytes and Chinese hamster livers. A subunit molecular weight of 26000--27000 as reported by other authors was obtained for both enzymes by gel electrophoresis in the presence of dodecylsulfate. Gradient gel electrophoresis revealed that the native enzymes mainly have a molecular weight of 105000--110000 and are thus apparently tetrameric, when held in the active state by the presence of phosphoribosyl diphosphate. The dimeric enzyme with a molecular weight of 52000--55000, was also found under other conditions. The trimer occurred only in the absence of phosphoribosyl diphosphate, for instance by glycerol gradient centrifugation. The enzyme from human erythrocytes was partly degraded during purification in the absence of a protease inhibitor. The purified enzyme has a very low protease contamination level. Proteolysis is an additional cause of heterogeneity and might therefore explain earlier conflicting results. Since the heterogeneous nature of hypoxanthine phosphoribosyltransferase is caused only by the secondary processes of dissociation/association and, in the case of the human erythrocyte enzyme, degradation, we suggest that the use of the term 'isozyme' to describe the different forms should be avoided.
 ...
PMID:Evidence against the existence of real isozymes of hypoxanthine phosphoribosyltransferase. 71 Apr 24

A triplex-forming oligonucleotide (TFO), HPRT3, conjugated to a psoralen derivative, was designed to target a psoralen reaction site within the HPRT gene. HPRT3 bound with high affinity to a synthetic duplex target sequence. At a uniform UVA radiation dose, the ratio of psoralen monoadducts (MA) to interstrand crosslinks decreased and inverted with increasing TFO concentration. As the TFO concentration increased from 10 nm to 10 microm, the efficiency of psoralen MA formation remained relatively constant but the efficiency of interstrand crosslink formation increased several-fold. Neither shortening the TFO to reduce its dissociation constant nor altering the DNA sequences flanking the TFO binding site altered the concentration dependence of MA and crosslink yields. The psoralen photokinetics associated with 10 nm HPRT3 converted to those associated with 10 microm HPRT3 with the addition of other unrelated TFOs at 10 microm that do not specifically interact with the HPRT3 target sequence. Glycerol at concentrations of 0.5% (vol/vol) or higher also mimicked high TFO concentrations in enhancing crosslink formation. These results demonstrate that while psoralen may be targeted to react at a particular sequence by TFOs, photoreactivity associated with triplex formation is also modulated by sequence-independent factors that may affect the local macromolecular environment.
 ...
PMID:Modulation of psoralen DNA crosslinking kinetics associated with a triplex-forming oligonucleotide. 1843 21