Mutations in the tetramer interface of human glucose-6-phosphate dehydrogenase reveals kinetic differences between oligomeric states

Autor(es)

Ranzani, Americo Tavares ; Cordeiro, Artur Torres

• Tipo de documento: Artigo Científico
• Fonte: FEBS LETTERS; v. 591, n. 9, p. 7-pg., 2017-05-01.

Resumo

Glucose-6-phosphate dehydrogenase (G6PDH) catalyzes the oxidation of glucose-6-phoshate to 6-phospho-gluconolactone with the concomitant reduction of NADP(+) to NADPH. In solution, the recombinant human G6PDH is known to be active as dimers and tetramers. To distinguish between the kinetic properties of dimers and tetramers of the G6PDH is not trivial. Steady-state kinetic experiments are often performed at low enzyme concentrations, which favor the dimeric state. The present work describes two novel human G6PDH mutants, one that creates four disulfide bonds among apposing dimers, resulting in a 'cross-linked' tetramer, and another that prevents the dimer to dimer association. The functional and structural characterizations of such mutants indicate the tetramer as the most active form of human G6PDH. (AU)

• Processo FAPESP: 12/23682-7 - Caracterização estrutural da enzima málica de Trypanosoma cruzi e descoberta de inibidores por ensaio de triagem de alto desempenho.
• Beneficiário: Américo Tavares Ranzani
• Modalidade de apoio: Bolsas no Brasil - Doutorado