Congresos y reuniones científicas
Título:
Insight into the basis of glycogenin inactivation causing glycogenosis by mutational approach
Autor/es:
CARRIZO, M.E.; ROMERO, J.M.; ISSOGLIO, F.M.; CURTINO, J.A.
Lugar:
Potrero de los Funes, San Luis
Reunión:
Congreso; XLVII Reunión Anual-SAIB; 2011
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
UDP-glucose 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.