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.
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