| Autor: |
NJÅLSSON, Runa, CARLSSON, Katarina, OLIN, Birgit, CARLSSON, Birgit, WHITBREAD, Lel, POLEKHINA, Galina, PARKER, Michael W., NORGREN, Svante, MANNERVIK, Bengt, BOARD, Philip G., LARSSON, Agne |
| Zdroj: |
Biochemical Journal; July 2000, Vol. 349 Issue: 1 p275-279, 5p |
| Abstrakt: |
Patients with hereditary glutathione synthetase (GS) (EC 6.3.2.3) deficiency present with variable clinical pictures, presumably related to the nature of the mutations involved. In order to elucidate the relationship between genotype, enzyme function and clinical phenotype, we have characterized enzyme kinetic parameters of missense mutations R125C, R267W, R330C and G464V from patients with GS deficiency. One of the mutations predominantly affected the Km value, with decreased affinity for glycine, two mutations influenced both Km and Vmax values, and one mutation reduced the stability of the enzyme. This characterization agrees well with predictions based on the recently reported crystal structure of human GS. Thus our data indicate that different mutations can affect the catalytic capacity of GS by decreasing substrate affinity, maximal velocity or enzyme stability. |
| Databáze: |
Supplemental Index |
| Externí odkaz: |
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