Hypoxanthine-guanine phosphoribosyl transferase with altered substrate affinity in mutant mouse lymphoma cells.
Cells with altered hypoxanthine-guanine phosphoribosyl transferase (HPRT) (IMP:pyrophosphate phosphoribosyltransferase, EC 2.4.2.8) have been selected. Compared to wild type, mutant enzyme has a reduced affinity for the substrate phosphoribosyl pyrophosphate and is more labile to heat inactivation. Mutant cells are resistant to 6-thioguanine at 33-39 degrees C and sensitive to hypoxanthine-aminopterin-thymidine at 37-39 degrees C, but not at 33 degrees C. We hypothesize that a single structural mutation of HPRT can explain these results.
D000630:Aminopterin / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D004351:Drug Resistance; D007041:Hypoxanthine Phosphoribosyltransferase / Q000378:metabolism*; D007042:Hypoxanthines / Q000378:metabolism; D008223:Lymphoma / Q000201:enzymology*; D051379:Mice; D009153:Mutagens / Q000494:pharmacology; D009154:Mutation; D010428:Pentosephosphates / Q000378:metabolism*; D010754:Phosphoribosyl Pyrophosphate / Q000378:metabolism*; D013696:Temperature; D013866:Thioguanine / Q000494:pharmacology; D013936:Thymidine / Q000378:metabolism
D007042:Hypoxanthines; D009153:Mutagens; D010428:Pentosephosphates; D010754:Phosphoribosyl Pyrophosphate; D007041:Hypoxanthine Phosphoribosyltransferase; D013866:Thioguanine; D000630:Aminopterin; D013936:Thymidine