3grt: Difference between revisions
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==Overview== | ==Overview== | ||
The substrate specificity of the human enzyme glutathione reductase was, changed from its natural substrate glutathione to trypanothione, [N1,N8-bis(glutathionyl)spermidine] by site-directed mutagenesis of two, residues. The glutathione analogue, trypanothione, is the natural, substrate for trypanothione reductase, an enzyme found in trypanosomatids, and leishmanias, the causative agents of diseases such as African sleeping, sickness, Chagas disease, and Oriental sore. The rational bases for our, mutational experiments were the availability of a high-resolution X-ray, structure for human glutathione reductase with bound substrates, the, active site sequence comparisons of human glutathione reductase and the, trypanothione reductases from Trypanosoma congolense and Trypanosoma, cruzi, a complementary set of mutants in T. congolense trypanothione, reductase, and the properties of substrate analogues of trypanothione., Mutation of two residues, A34----E34 and R37----W37, in the, glutathione-binding site of human glutathione reductase switches human, glutathione reductase into a trypanothione reductase with a preference for, trypanothione over glutathione by a factor of 700 using kcat/Km as a, criterion. | The substrate specificity of the human enzyme glutathione reductase was, changed from its natural substrate glutathione to trypanothione, [N1,N8-bis(glutathionyl)spermidine] by site-directed mutagenesis of two, residues. The glutathione analogue, trypanothione, is the natural, substrate for trypanothione reductase, an enzyme found in trypanosomatids, and leishmanias, the causative agents of diseases such as African sleeping, sickness, Chagas disease, and Oriental sore. The rational bases for our, mutational experiments were the availability of a high-resolution X-ray, structure for human glutathione reductase with bound substrates, the, active site sequence comparisons of human glutathione reductase and the, trypanothione reductases from Trypanosoma congolense and Trypanosoma, cruzi, a complementary set of mutants in T. congolense trypanothione, reductase, and the properties of substrate analogues of trypanothione., Mutation of two residues, A34----E34 and R37----W37, in the, glutathione-binding site of human glutathione reductase switches human, glutathione reductase into a trypanothione reductase with a preference for, trypanothione over glutathione by a factor of 700 using kcat/Km as a, criterion. | ||
==Disease== | |||
Known disease associated with this structure: Hemolytic anemia due to glutathione reductase deficiency OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=138300 138300]] | |||
==About this Structure== | ==About this Structure== | ||
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[[Category: oxidoreductase]] | [[Category: oxidoreductase]] | ||
''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov | ''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 23:48:27 2007'' | ||
