7zvd | pdb_00007zvd
K89 acetylated glucose-6-phosphate dehydrogenase (G6PD) in a complex with structural NADP+
Structural highlights
DiseaseG6PD_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] FunctionG6PD_HUMAN Produces pentose sugars for nucleic acid synthesis and main producer of NADPH reducing power. Publication Abstract from PubMedLysine 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
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