Identification of the binding domain for NADP sup + of human glucose-6-phosphate dehydrogenase by sequence analysis of mutants

Journal Article · Fri Dec 01 00:00:00 EST 1989 · Proceedings of the National Academy of Sciences of the United States of America; (USA)

DOI:https://doi.org/10.1073/pnas.86.24.10015· OSTI ID:6921551

Hirono, A; Kuhl, W; Gelbart, T; Forman, L; Beutler, E ^[1]; Fairbanks, V F ^[2]

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1. Scripps Clinic and Research Foundation, La Jolla, CA (USA)
2. Mayo Clinic, Rochester, MN (USA)

Human erythrocyte glucose-6-phosphate is normally quite stable in the presence of 10 {mu}M NADP{sup +}. Certain glucose-6-phosphate dehydrogenase variants lose virtually all their activity at this concentration of NADP{sup +} but are reactivated by 200 {mu}M NADP{sup +}. Such variants presumably have a defect in their NADP{sup +}-binding site. The authors 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{sup +}. Six patients had 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 Drosophila. The anomalous electrophoretic behavior of some of the variants can be explained by their loss of ability to bind NADP{sup +}. The conclude that the region in which these mutations occur defines the binding domain for NADP{sup +} and that binding NADP{sup +} that has been designated as structural and as catalytic probably occurs at the same site.

• OSTI ID: 6921551
• Journal Information: Proceedings of the National Academy of Sciences of the United States of America; (USA), Vol. 86:24; ISSN 0027-8424
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
HEMIACETAL DEHYDROGENASES
AMINO ACID SEQUENCE
HEREDITARY DISEASES
BIOCHEMISTRY
RECOMBINANT DNA
DNA SEQUENCING
ANEMIAS
BIOCHEMICAL REACTION KINETICS
ELECTROPHORESIS
ERYTHROCYTES
MAN
MUTANTS
NADP
PATIENTS
PHOSPHORUS 32
ANIMALS
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BIOLOGICAL MATERIALS
BLOOD
BLOOD CELLS
BODY FLUIDS
CHEMISTRY
COENZYMES
DAYS LIVING RADIOISOTOPES
DISEASES
DNA
ENZYMES
HEMIC DISEASES
ISOTOPES
KINETICS
LIGHT NUCLEI
MAMMALS
MATERIALS
MOLECULAR STRUCTURE
NUCLEI
NUCLEIC ACIDS
NUCLEOTIDES
ODD-ODD NUCLEI
ORGANIC COMPOUNDS
OXIDOREDUCTASES
PHOSPHORUS ISOTOPES
PRIMATES
RADIOISOTOPES
REACTION KINETICS
STRUCTURAL CHEMICAL ANALYSIS
SYMPTOMS
VERTEBRATES
550201* - Biochemistry- Tracer Techniques