ROMERO JORGE MIGUEL
Congresos y reuniones científicas
Título:
Structural effects of a mutation responsible for a glycogenin related novel glycogen storage disease
Autor/es:
CARRIZO, MARÍA E; ROMERO, JORGE M.; ISSOGLIO, FEDERICO M.; CURTINO, JUAN A.
Lugar:
Puerto Madryn
Reunión:
Congreso; XLVI Reunión Anual de la Sociedad Argentina de Investigación Bioquímica y Biología Molecular (SAIB); 2010
Institución organizadora:
Sociedad Argentina de Investigación Bioquímica y Biología Molecular (SAIB)
Resumen:
Glycogen Storage Diseases (GSD) are inherited metabolic disorders of glycogen metabolism. They are classified based on the enzyme deficiency and the affected tissue. The most recently described GSD is due to the deficiency of glycogenin-1, caused by a Thr82Met mutation. Glycogenin is a self-glucosylating protein involved in the initiation of glycogen synthesis. In the presence of UDP-glucose and Mn+2 it catalyzes the formation of a short glucose polymer covalently attached to its Tyr194 hydroxyl group. Glycogenin-1 is one of the two human glycogenin isoforms and is mainly expressed in muscle. The second isoform, glycogenin-2, is the liver protein. Human glycogenin-1 displays 93% identity with rabbit skeletal muscle glycogenin, the best studied member of this protein family and the only one whose three dimensional structure has been solved. Thr82 is not only present in human and rabbit glycogenins, it is also conserved in many members of the family. According to the reaction mechanism proposed for the protein, this residue would not be directly involved neither in catalysis nor in substrate binding. To explore the reasons for Thr82Met mutation induced loss of function, we have prepared this mutant form of rabbit glycogenin. We report here, the crystal structure of apo- and UDP-glucose/Mn+2 bound Thr82Met mutant and the comparison of these results with those of the wild type enzyme