Identification of the binding domain for NADP+ of human glucose-6-phosphate dehydrogenase by sequence analysis of mutants.
- 1 December 1989
- journal article
- research article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences
- Vol. 86 (24) , 10015-10017
- https://doi.org/10.1073/pnas.86.24.10015
Abstract
Huamn erythrocyte glucose-6-phosphate dehydrogenase is normally quite stable in the presence of 10 .mu.M NADP+. Certain glucose-6-phosphate dehydrogenase variants lose virtually all their activity at this concentration of NADP+ but are reactivated by 200 .mu.M NADP+. Such variants presumably have a defect in their NADP+-binding site. We analyzed the sequence of cDNA or genomic DNA from seven unrelated patients with hemolytic anemia due to the inheritance of variants that are reactivated by NADP+. Six patients has substitutions of one of three adjacent amino acids, and the seventh patient had another amino acid substitution 23 residues downstream. These amino acids are highly conserved, all being present in rat and all but one being found also in Drosphila. The anomalous electrophoretic behavior of some of the variants can be explained by their loss of ability to bind NADP+. We conclude that the region in which these mutations occur defines the binding domain for NADP+ and that binding NADP+ that has been designated as "structural" and as "catalytic" probably occurs at the same site.This publication has 19 references indexed in Scilit:
- Genetic Variation of Glucose-6-Phosphate DehydrogenaseMedicine, 1988
- Diverse point mutations in the human glucose-6-phosphate dehydrogenase gene cause enzyme deficiency and mild or severe hemolytic anemia.Proceedings of the National Academy of Sciences, 1988
- Nucleotide sequence of the Drosophila glucose-6-phosphate dehydrogenase gene and comparison with the homologous human geneGene, 1988
- Cloning and sequence of a cDNA encoding rat glucose-6-phosphate dehydrogenaseNucleic Acids Research, 1988
- Detection of sickle cell anaemia and thalassaemiasNature, 1987
- Isolation of biologically active ribonucleic acid from sources enriched in ribonucleaseBiochemistry, 1979
- DNA sequencing with chain-terminating inhibitorsProceedings of the National Academy of Sciences, 1977
- Human erythrocyte glucose 6-phosphate dehydrogenase. Content of bound coenzymeBiochemical and Biophysical Research Communications, 1974
- Active molecular unit and NADP content of human glucose 6-phosphate dehydrogenaseBiochemical and Biophysical Research Communications, 1970
- Hybridization of Glucose-6-Phosphate Dehydrogenase from Rat and Human ErythrocytesScience, 1965