Mechanistic and Metabolic Inferences from the Binding of Substrate Analogues and Products to Arginase
| Autor: | David E. Ash, J.D. Cox, S. Pethe, Jean-Luc Boucher, David W. Christianson, Daniel Mansuy, E. Cama, Diana M. Colleluori |
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| Rok vydání: | 2001 |
| Předmět: | |
| Zdroj: | Biochemistry. 40:2689-2701 |
| ISSN: | 1520-4995 0006-2960 |
| DOI: | 10.1021/bi002318+ |
| Popis: | Arginase is a binuclear Mn2+ metalloenzyme that catalyzes the hydrolysis of l-arginine to l-ornithine and urea. X-ray crystal structures of arginase complexed to substrate analogues Nω-hydroxy-l-arginine and Nω-hydroxy-nor-l-arginine, as well as the products l-ornithine and urea, complete a set of structural “snapshots” along the reaction coordinate of arginase catalysis when interpreted along with the X-ray crystal structure of the arginase-transition-state analogue complex described in Kim et al. [Kim, N. N., Cox, J. D., Baggio, R. F., Emig, F. A., Mistry, S., Harper, S. L., Speicher, D. W., Morris, Jr., S. M., Ash, D. E., Traish, A. M., and Christianson, D. W. (2001) Biochemistry 40, 2678−2688]. Taken together, these structures render important insight on the structural determinants of tight binding inhibitors. Furthermore, we demonstrate for the first time the structural mechanistic link between arginase and NO synthase through their respective complexes with Nω-hydroxy-l-arginine. That Nω-hydroxy-l-a... |
| Databáze: | OpenAIRE |
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