1,721,195 research outputs found
Optimization of D-amino acid oxidase for low substrate concentrations--towards a cancer enzyme therapy.
No full textd-Amino acid oxidase (DAAO) has recently become of interest as a biocatalyst for industrial applications and for therapeutic treatments. It has been used in gene-directed enzyme prodrug therapies, in which its production of H(2)O(2) in tumor cells can be regulated by administration of substrate. This approach is limited by the locally low O(2) concentration and the high K(m) for this substrate. Using the directed evolution approach, one DAAO mutant was identified that has increased activity at low O(2) and d-Ala concentrations and a 10-fold lower K(m) for O(2). We report on the mechanism of this DAAO variant and on its cytotoxicity towards various mammalian cancer cell lines. The higher activity observed at low O(2) and d-Ala concentrations results from a combination of modifications of specific kinetic steps, each being of small magnitude. These results highlight the potential in vivo applicability of this evolved mutant DAAO for tumor therapy
X-ray studies of recombinant rat kidney long-chain hydroxy acid oxidase and of the recombinant flavin-binding domain of bakers yeast flavocytochrome b2
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Analysis of the redox properties of the human diflavin enzyme NADPH-cytochrome P450 reductase and its domains
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