Mutational analysis of the structure and function of the adenine phosphoribosyltransferase enzyme of Chinese hamster.
We have analyzed the adenine phosphoribosyltransferase (APRT) enzyme from Chinese hamster ovary cells through the study of mutants that are able to grow in the presence of the toxic adenine analogue 8-azaadenine. The distribution of the amino acid alterations was analyzed in terms of the binding regions for the purine and phosphoribosylpyrophosphate substrates and a comparison was made with mutants known in human APRT and human, mouse and hamster hypoxanthine-guanine phosphoribosyltransferase. A number of mutants were found to cluster in several regions of the amino acid sequence. Residual enzyme activity with adenine was determined and this was correlated with substrate binding regions. A model of the secondary structure features is proposed.
de Boer
J G
JG
York University Biology Department, Downsview, Ontario, Canada.
Glickman
B W
BW
D000228:Adenine Phosphoribosyltransferase / Q000235:genetics* / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002460:Cell Line; D006224:Cricetinae; D004252:DNA Mutational Analysis; D008969:Molecular Sequence Data; D009154:Mutation; D010754:Phosphoribosyl Pyrophosphate / Q000378:metabolism; D011487:Protein Conformation; D016415:Sequence Alignment; D013329:Structure-Activity Relationship
D010754:Phosphoribosyl Pyrophosphate; D000228:Adenine Phosphoribosyltransferase