INVESTIGADORES
ISSOGLIO Federico Matias
congresos y reuniones científicas
Título:
Insigth into the basis of glycogenin inactivation causing glycogenosis by mutational approach
Autor/es:
CARRIZO MARÍA E.; ROMERO, JORGE M.; ISSOGLIO, FEDERICO M.; CURTINO, JUAN A.
Lugar:
Potrero de los Funes, San Luis
Reunión:
Congreso; XLVII Reunión Anual de la Sociedad Argentina de Investigación Bioquímica y Biología Molecular (SAIB); 2011
Institución organizadora:
Sociedad Argentina de Investigación Bioquímica y Biología Molecular (SAIB)
Resumen:
Glycogenin-1 is one of the two human glycogenin isoforms, mainly
expressed in muscle. It displays 93% sequence identity with the
rabbit enzyme, the best studied member of this protein family and
the only one whose three dimensional structure has been solved. A
missense mutation, Thr82Met, in one allele of the glycogenin-1
gene GYG1, producing human glycogenin inactivation and
deficient priming of glycogen synthesis, was recently described. To
analyze the structural basis of the loss of enzyme activity
responsible for the human glycogenosis phenotype, we introduced
the Thr82Met mutation into rabbit muscle glycogenin and solved its
crystal structure. Thr82Met substitution resulted in only a few
altered intramolecular residues interactions, while those with UDPglucose were conserved. The results are consistent with the enzyme
inactivation due to the prevented essential involvement of Asp162
in UDP-glucose activation, produced by loss of Thr82 to Asp162
hydrogen bonding, favored hydrophobic interactions between the
replacing methionine and the neighboring amino acids, or both.
Here we report the characterization of glycogenin mutants obtained
by substitution of Thr82 with residues of different size and
hydrophobicity, in an attempt to distinguish between the above
proposed causes of inactivation