Structural and biochemical insight into glycogenin inactivation by the glycogenosis-causing T82M mutation

CARRIZO, MARÍA E.; ROMERO, JORGE M.; ISSOGLIO, FEDERICO M.; CURTINO, JUAN A.

FEBS LETTERS

ELSEVIER SCIENCE BV

Lugar: Amsterdam; Año: 2012 vol. 586 p. 254 - 257

0014-5793

The X-ray structure of rabbit glycogenin containing the T82M (T83M according to previous authors amino acid numbering) mutation causing glycogenosis showed the loss of Thr82 hydrogen bond to Asp162, the residue involved in the activation step of the glucose transfer reaction mechanism. Autoglucosylation, maltoside transglucosylation and UDP-glucose hydrolyzing activities were abolished even though affinity and interactions with UDP-glucose and positioning of Tyr194 acceptor were conserved. Substitution of Thr82 for serine but not for valine restored the maximum extent of autoglucosylation as well as transglucosylation and UDP-glucose hydrolysis rate. Results provided evidence sustaining the essential role of the lost single hydrogen bond for UDP-glucose activation leading to glycogenin-bound glycogen primer synthesis.