| Autor: |
David N. Silverman, James R. Zucali, Amy S. Hearn, Anupam Agarwal, Harry S. Nick, Jorge E. Garcia, Vincent Leveque, Bradley S. Fletcher, Christopher A. Davis, J. Andres Melendez, Justin S. Bickford |
| Rok vydání: |
2004 |
| Předmět: |
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| Zdroj: |
Journal of Biological Chemistry. 279:12769-12776 |
| ISSN: |
0021-9258 |
| DOI: |
10.1074/jbc.m310623200 |
| Popis: |
Mn-SOD serves as the primary cellular defense against oxidative damage by converting superoxide radicals () to O2 and H2O2. A unique characteristic of this mitochondrial anti-oxidant enzyme is the conservation from bacteria to man of a rapidly formed product inhibited state. Using site-directed mutagenesis, we have generated an active site mutant (H30N) of human Mn-SOD, which exhibits significantly reduced product inhibition and increased enzymatic efficiency. Overexpression of the H30N enzyme causes anti-proliferative effects in vitro and anti-tumor effects in vivo. Our results provide a teleological basis for the phylogenetically invariant nature of position His-30 and the evolutionary conservation of product inhibition. These data also provide more direct intracellular evidence for the signaling role associated with H2O2. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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