Entrapment and Inhibition of Human Immunodeficiency Virus Proteinase by α₂-Macroglobulin and Structural Changes in the Inhibitor

抄録

The inhibitory effect of α₂-macroglobulin (α₂M), a major plasma proteinase inhibitor, on human immunodeficiency virus (HIV) proteinase was investigated. The activity of HIV proteinase toward the Moloney murine sarcoma virus-derived gag protein (a highmolecular-mass substrate) was found to be inhibited by α₂M at pH 5.5-7.4. On the other hand, the activity toward the B chain of oxidized insulin (a low- molecular-mass substrate) was scarcely inhibited. The complex of α₂M and HIV proteinase was isolated by gel filtration and the enzyme was shown to be significantly protected by the complex formation from autoinactivation under nonreducing conditions. The stoichiometry of the complex formation was found to be 2:1 (enzyme:α₂M, mol/mol). These results demonstrate the entrapment and concomitant inhibition of HIV proteinase by α₂M.