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Inhibitor stabilization of human immunodeficiency virus type-2 proteinase dimer formation
T F Holzman1, W E Kohlbrenner, D Weigl
1Protein Biochemistry Research, Abbott Laboratories, Abbott Park, Illinois 60064.
The Journal of Biological Chemistry
|October 15, 1991
Summary
Researchers directly observed human immunodeficiency virus type-2 (HIV-2) proteinase self-association. Inhibitors stabilize the active dimer form, suggesting a model for viral assembly.
Area of Science:
- Biochemistry
- Structural Biology
- Virology
Background:
- Human immunodeficiency virus type-2 (HIV-2) proteinase is crucial for viral maturation.
- Understanding proteinase self-association is key to developing effective inhibitors.
Purpose of the Study:
- To directly observe the subunit self-association behavior of purified recombinant HIV-2 proteinase.
- To investigate the effect of a peptidomimetic inhibitor on proteinase self-association.
Main Methods:
- Sedimentation equilibrium analytical ultracentrifugation was employed.
- Experiments were conducted at 8.8°C and two pH values, with and without inhibitor.
Main Results:
- HIV-2 proteinase exhibited monomer-dimer-tetramer self-association behavior.
- Inhibitor presence favored dimer formation and disfavored tetramer formation.
- Inhibitor binding decreased the dissociation constant for dimer formation by 5-14 fold.
Conclusions:
- Inhibitor binding stabilizes the active dimeric form of HIV-2 proteinase.
- This stabilization supports a model of substrate-induced formation of active proteinase dimers during virion assembly.