Structural highlights
Disease
G6PD_HUMAN Defects in G6PD are the cause of chronic non-spherocytic hemolytic anemia (CNSHA) [MIM:305900. Deficiency of G6PD is associated with hemolytic anemia in two different situations. First, in areas in which malaria has been endemic, G6PD-deficiency alleles have reached high frequencies (1% to 50%) and deficient individuals, though essentially asymptomatic in the steady state, have a high risk of acute hemolytic attacks. Secondly, sporadic cases of G6PD deficiency occur at a very low frequencies, and they usually present a more severe phenotype. Several types of CNSHA are recognized. Class-I variants are associated with severe NSHA; class-II have an activity <10% of normal; class-III have an activity of 10% to 60% of normal; class-IV have near normal activity.[1]
Function
G6PD_HUMAN Produces pentose sugars for nucleic acid synthesis and main producer of NADPH reducing power.
Publication Abstract from PubMed
Lysine acetylation has been discovered in thousands of non-histone human proteins, including most metabolic enzymes. Deciphering the functions of acetylation is key to understanding how metabolic cues mediate metabolic enzyme regulation and cellular signaling. Glucose-6-phosphate dehydrogenase (G6PD), the rate-limiting enzyme in the pentose phosphate pathway, is acetylated on multiple lysine residues. Using site-specifically acetylated G6PD, we show that acetylation can activate (AcK89) and inhibit (AcK403) G6PD. Acetylation-dependent inactivation is explained by structural studies showing distortion of the dimeric structure and active site of G6PD. We provide evidence for acetylation-dependent K95/97 ubiquitylation of G6PD and Y503 phosphorylation, as well as interaction with p53 and induction of early apoptotic events. Notably, we found that the acetylation of a single lysine residue coordinates diverse acetylation-dependent processes. Our data provide an example of the complex roles of acetylation as a posttranslational modification that orchestrates the regulation of enzymatic activity, posttranslational modifications, and apoptotic signaling.
Acetylation-dependent coupling between G6PD activity and apoptotic signaling.,Wu F, Muskat NH, Dvilansky I, Koren O, Shahar A, Gazit R, Elia N, Arbely E Nat Commun. 2023 Oct 5;14(1):6208. doi: 10.1038/s41467-023-41895-2. PMID:37798264[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Beutler E, Westwood B, Prchal JT, Vaca G, Bartsocas CS, Baronciani L. New glucose-6-phosphate dehydrogenase mutations from various ethnic groups. Blood. 1992 Jul 1;80(1):255-6. PMID:1611091
- ↑ Wu F, Muskat NH, Dvilansky I, Koren O, Shahar A, Gazit R, Elia N, Arbely E. Acetylation-dependent coupling between G6PD activity and apoptotic signaling. Nat Commun. 2023 Oct 5;14(1):6208. PMID:37798264 doi:10.1038/s41467-023-41895-2
