Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P00492 (hypoxanthine-guanine phosphoribosyltransferase)
 2,385 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The binding of ligands to proteins can be enhanced through improved packing within the proteins that may, or may not, occur with conformational change. Enzymes can similarly improve their catalytic magic through better packing in the transition state (TS) for reaction. In principle, the improved packing demands no more than the minute shortening of non-covalent interactions throughout much of the structure of the protein (positively cooperative binding). Improved protein packing can account for the remarkably high biotin/streptavidin affinity, and perhaps also for a major part of the catalytic function of hypoxanthine-guanine phosphoribosyltransferase and purine nucleoside phosphorylase (PNP). As successive NAD(+) molecules bind to the glyceraldehyde phosphate dehydrogenase tetramer, they do so with positively cooperative binding (using the term as applied in crystallization and protein folding) that decreases at each step. This binding is negatively cooperative in the usage stemming from Monod and co-workers.
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PMID:Enzyme catalysis from improved packing in their transition-state structures. 2081 Mar 4

Chinese hamster x American mink somatic cell hybrids were obtained and examined for chromosome content and expression of mink malate dehydrogenase, NADP (MOD-1; EC 1.1.1.40), malate dehydrogenase, NAD (MOR-1; EC 1.1.1.37), glucose-6-phosphate dehydrogenase (G6PD; EC 1.1.1.49) and hypoxanthine phosphoribosyltransferase (HPRT; EC 2.4.2.8). All the hybrid clones examined were found to segregate mink chromosomes. A clone panel containing 25 clones was set up. The possibilities and limitations of this panel for mink gene mapping are analysed. Using this panel, it is feasible to rapidly map genes located on chromosomes 1-13 and to provisionally assign genes located on chromosome 14 and the X. Based on the data obtained, the genes for MOD-1 and MOR-1 were firmly assigned to mink chromosomes 1 and 11, respectively, and the genes for G6PD and HPRT were provisionally assigned to the X.
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PMID:Chinese hamster x American mink somatic cell hybrids: characterization of a clone panel and assignment of the mink genes for malate dehydrogenase, NADP-1 and malate dehydrogenase, NAD-1. 2427 32

Although xanthinuria is nonfatal in human, xanthine oxidoreductase knockout (Xor-KO) mice have only a short lifespan. Hypoxanthine phosphoribosyltransferase activity (HPRT) in human and wild mice is higher than in laboratory mice. The aim of this study was to investigate the underlying mechanisms that give rise to the longer lifespan of high-HPRT/Xor-KO mice. Before Xor-KO mice die, urinary excretion of hypoxanthine increased with a corresponding decrease in excretion of xanthine. The switch of excretion from xanthine to hypoxanthine might be a cause of death for Xor-KO mice, suggesting inhibition of NAD+-dependent IMP dehydrogenase. Because hypoxanthine inhibits the synthesis of nicotinamide mononucleotide (NMN), a precursor of NAD+, the accumulation of hypoxanthine in Xor-KO mice may cause a depletion in the levels of NAD+. Moreover, urinary excretion of urate in high-HPRT/Uox-KO/Xor-KO mice means urate derived from gut microbiota is absorbed by the intestine. Likewise, over excretion of oxypurine in mice may be caused by intestinal absorption of oxypurine. For NAD+ replenishment, oral supplementation with 1% L-tryptophan, an alternative precursor of NAD+, resulted in a recovery of body weight gain in high-HPRT/Uox-KO/Xor-KO mice. In conclusion, the death of Xor-KO mice by renal failure seems to be caused by a depletion in NAD+ levels due to the intracellular accumulation of hypoxanthine. NAD+ replenishment by oral supplementation of NMN or tryptophan was complicated by the effect of gut microbiota and failed to rescue high-HPRT/Xor-KO mice. The attenuation of intestinal absorption of oxypurines seems to be necessary to avoid hypoxanthine accumulation and over excretion of oxypurine.
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PMID:Xanthine oxidoreductase knockout mice with high HPRT activity were not rescued by NAD+ replenishment. 3212 84


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