Zinc inhibition of renin and the protease from human immunodeficiency virus type 1
| Autor: | Zhong Yin Zhang, Kathy L. O'Connell, Alfredo G. Tomasselli, John O. Hui, Roger A. Poorman, Ilene M. Reardon, Robert L. Heinrikson |
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| Rok vydání: | 1991 |
| Předmět: |
inorganic chemicals
medicine.medical_treatment Molecular Sequence Data Biochemistry Catalysis Cell Line Non-competitive inhibition Cricetulus Cricetinae Renin–angiotensin system Renin medicine HIV Protease Inhibitor Animals Humans Amino Acid Sequence chemistry.chemical_classification Protease biology Chemistry Substrate (chemistry) HIV Protease Inhibitors Hydrogen-Ion Concentration enzymes and coenzymes (carbohydrates) Kinetics Zinc Enzyme Cell culture Enzyme inhibitor biology.protein HIV-1 Protein Binding |
| Zdroj: | Biochemistry. 30(36) |
| ISSN: | 0006-2960 |
| Popis: | We report here for the first time that Zn2+ is an effective inhibitor of renin and the protease from HIV-1, two aspartyl proteinases of considerable physiological importance. Inhibition of renin is noncompetitive and is accompanied by binding of 1 mol of Zn2+/mol of enzyme. Depending on the substrate, inhibition of the HIV protease by Zn2+ can be either competitive or noncompetitive, but in neither case is loss of activity due to disruption of the protease dimer. Inhibition of both enzymes is first order with respect to Zn2+ and is rapidly reversed by addition of EDTA. Ki values are strongly pH dependent and optimal in the range of 20 microM at or above pH 7. All of the data in hand suggest that the inhibitory effect of Zn2+ is a consequence of its binding at, or near, the active-site carboxyl groups of these aspartyl proteinases. This inhibition of the viral enzyme may help to explain some of the beneficial effects seen in AIDS patients who have received Zn2+ therapy. |
| Databáze: | OpenAIRE |
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