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Dimerization and activation of the herpes simplex virus type 1 protease
1Department of Antiviral Research, Merck Research Laboratories, West Point, Pennsylvania 19486, USA.
The Journal of Biological Chemistry
|March 21, 1997
Summary
The herpes simplex virus type 1 (HSV-1) protease requires dimerization to become catalytically active. Specific cosolvents enhance this dimerization, increasing enzyme activity and mimicking activation seen in other herpesvirus proteases.
Area of Science:
- Biochemistry
- Virology
- Enzymology
Background:
- Herpes simplex virus type 1 (HSV-1) protease is a key viral enzyme.
- Understanding its quaternary structure is crucial for its catalytic function.
Purpose of the Study:
- To investigate the relationship between the quaternary state of HSV-1 protease and its catalytic activity.
- To elucidate the mechanism of activation by antichaotropic cosolvents.
Main Methods:
- Size-exclusion chromatography to analyze monomer-dimer equilibrium.
- Enzyme activity assays on isolated monomeric and dimeric species.
- Kinetic analysis under various solvent conditions.
Main Results:
- HSV-1 protease exists in a monomer-dimer equilibrium.
- The dimeric form of the enzyme is catalytically active.
- Antichaotropic cosolvents (glycerol, citrate, phosphate) promote dimerization and activate the protease.
- Activation potency correlates with dimerization efficiency.
Conclusions:
- Dimerization is essential for HSV-1 protease activity.
- Activation by cosolvents is mediated by enhanced dimerization.
- The activation mechanism is analogous to that of human cytomegalovirus protease.