Synergistic binding of inhibitors to the protease from HIV type 1
| Autor: | Ernest Asante-Appiah, William W.-C. Chan |
|---|---|
| Rok vydání: | 1996 |
| Předmět: |
Proteases
Conformational change medicine.medical_treatment Molecular Sequence Data Human immunodeficiency virus (HIV) Biology medicine.disease_cause Biochemistry Antiviral Agents Drug synergism HIV Protease medicine Aspartic Acid Endopeptidases Amino Acid Sequence Molecular Biology Peptide sequence chemistry.chemical_classification Protease Substrate (chemistry) Drug Synergism Cell Biology HIV Protease Inhibitors Peptide Fragments Kinetics Enzyme chemistry HIV-1 Research Article |
| Zdroj: | The Biochemical journal. 315 |
| ISSN: | 0264-6021 |
| Popis: | Inhibition of the protease in HIV is a potentially useful approach for the treatment of AIDS. In the course of evaluating inhibitors of the HIV-1 protease, we observed a strong synergism between certain inhibitors that might be expected to bind to different sites in this enzyme. The binding affinity of carbobenzyloxyisoleucinylphenylalaninol, for example, is increased 125-fold in the presence of carbobenzyloxyglutaminylisoamylamide. These synergistic effects between inhibitors have specific structural requirements that correlate well with the known substrate preference of the enzyme. The molecular basis for this phenomenon remains to be elucidated but it could involve substrate-induced conformational change as part of the reaction mechanism. Similar effects have been reported previously for several zinc proteases. Thus this work extends the observation to a different class of enzymes and suggests that the phenomenon might be widespread. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
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