ROMERO JORGE MIGUEL
Congresos y reuniones científicas
Título:
Novel structural insights into glycogenin catalytic mechanism
Autor/es:
CARRIZO, M E; ISSOGLIO FM; ROMERO JM; CURTINO JA
Lugar:
Ciudad de Buenos Aires
Reunión:
Simposio; First Argentinian Symposium of Glycobiology "GlycoAR 2014"; 2014
Institución organizadora:
Fundación Instituto Leloir
Resumen:

Glycogenin is the autoglucosyltransferase that initiates the polymerization of glucose to prime the de novo biosynthesis of glycogen. Its 3D structure and studies by gel filtration indicated that the enzyme exists in solution mainly as dimer. Based on kinetic studies it was proposed that autoglucosylation might occur by intradimer intersubunit glucosylation. However, we demonstrated that it could also exist as a monomer at lower concentrations and that this species is able to autoglucosylate by an intramolecular mechanism. Then, we evaluated if an intrasubunit glucosylation mechanism might also be involved in dimer autoglucosylation. We conclude that both, intrasubunit and intersubunit reaction mechanisms are necessary for the dimeric enzyme to acquire maximum autoglucosylation.

The requirement of glycogenin to initiate de novo polysaccharide biosynthesis became more evident with the report of a metabolic disorder associated with glycogen depletion caused by a mutation in glycogenin-1 gene, one of the human enzyme isoforms. The mutation results in the expression of the inactive Thr82Met glycogenin mutant. We introduced the mutation into rabbit muscle glycogenin and solved its crystal structure. The structure and the functional studies carried out in Thr82Ser and Thr82Val mutants revealed the critical role of a single hydrogen bond to Asp162 which is lost when Thr is replaced by Met.