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

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

ELSEVIER SCIENCE BV

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

he X-ray structure of rabbit glycogenin containing the T82M (T83M according to previous authors amino acid numbering [1]) 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.