Triosephosphate isomerase deficiency: effect of F240L mutation on enzyme structure

ROMERO, JORGE M

ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS

ELSEVIER SCIENCE INC

Lugar: Amsterdam; Año: 2020 vol. 689

0003-9861

Elevenmissense mutations have been describe in human triosephosphate isomerase (TPI),affecting its catalytic function. Several of these mutations generatetriosephosphate isomerase deficiency, the consequences of which can in somecases be lethal. The missense F240L mutation was found in a Hungarian patientshowing symptoms of chronic hemolytic anemia and neuromuscular dysfunction. In vitro studies using a recombinantversion of this mutant showed that it affects kinetic parameters, thermalstability and dimeric stability. Using X-ray crystal structures, the presentpaper describes how this mutation affected the flexibility of catalyticresidues K13 and part of the (β/α) 8-barrel fold facing the dimeric interface inthe TPI