Autor: |
M E, Popov, I V, Kashparov, L D, Rumsh, E M, Popov |
Rok vydání: |
1999 |
Předmět: |
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Zdroj: |
Bioorganicheskaia khimiia. 25(6) |
ISSN: |
0132-3423 |
Popis: |
A set of conformations was shown to be characteristic of the free-state spatial structure of substrate-like inhibitor JG-365 for aspartic protease from HIV-1. Among them, the lowest-energy conformations have a folded form of the peptide backbone. The inhibitor has a noncleavable hydroxyethylamine group with an additional chiral center in its structure. Our calculations showed that only the S-isomer of the inhibitor displays conformational characteristics that practically coincide with those of the native substrate for HIV-1 protease. One of the calculated conformations with a completely extended main chain and a relative energy of 9.5 kcal/mol very closely mimics the experimentally observed structure of the inhibitor in the enzyme-inhibitor complex. The realization of this structure is unlikely for a free inhibitor, because it has only a small number of interresidual noncovalent interactions in the extended conformation; these are presumably compensated for by intermolecular interactions at the active site of the enzyme. |
Databáze: |
OpenAIRE |
Externí odkaz: |
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