Substitution of arginine 219 by glycine compromises stability, dimerization, and catalytic activity in a G6PD mutant.

ABSTRACT: Glucose-6-phosphate dehydrogenase (G6PD) deficiency is one of the most common enzymopathies in humans, present in approximately half a billion people worldwide. More than 230 clinically relevant G6PD mutations of different classes have been reported to date. We hereby describe a patient with chronic hemolysis who presents a substitution of arginine by glycine at position 219 in G6PD protein. The variant was never described in an original publication or characterized on a molecular level. In the present study, we provide structural and biochemical evidence for the molecular basis of its pathogenicity. When compared to the wild-type enzyme, the Arg219Gly mutation markedly reduces the catalytic activity by 50-fold while having a negligible effect on substrate binding affinity. The mutation pr

SUBMITTER: Zgheib O 

PROVIDER: S-EPMC10709299 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature