Biochemical characterization of the glycogen storage disease-associated A16P mutant of glycogenin

MUÑOZ SOSA, CHRISTIAN J.; CURTINO, JUAN A.; CARRIZO, MARÍA E.

Villa General Belgrano, Córdoba, Argentina

Simposio; Second Argentinian Symposium on Glycobiology "GlycoAR 2016"; 2016

Glycogen storage diseases (GSD) are inherited metabolic disorders of glycogen metabolism characterized by accumulation of the polysaccharide with abnormal chemical structure or in an abnormal amount. GSD type 15 is an extremely rare genetic disorder reported only in a few patients to date. It is caused by mutations in the GYG1 gene, which encodes glycogenin-1, one of the isoforms of human glycogenin, the enzyme that initiates glycogen biosynthesis. One of the recently described cases (1) corresponds to a patient that was homozygous for an N-terminal missense variant (c.46G>C, p.Ala16Pro). The patient exhibited skeletal myopathy with storage of polyglucosan in muscle fibers and no cardiac involvement.Ala16 is conserved in many members of glycogenin family, thus, it was of interest to analyze the effect of its substitution on the catalytic properties of the protein in order to understand its role in the pathology. Since human and rabbit glycogenin amino acid sequences are 93% identical, we have introduced Ala16Pro mutation into rabbit enzyme and expressed the mutant in E. coli. In this work, we present the analysis of the effect of the mutation on the autoglucosylation, transglucosylation and UDP-glucose hydrolytic activities of the protein and on its substrate binding affinity.1. Malfatti, E., et al. (2014) Annals of neurology 76, 891-898.