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

The inhibitory effect of α2-macroglobulin (α2M), a major plasma proteinase inhibitor, on human immunodeficiency virus (HTV) proteinase was investigated. The activity of HTV proteinase toward the Moloney murine sarcoma virus-derived gag protein (a highmolecular-mass substrate) was found to be inhibited by a2M 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 a2M and HlV proteinase was isolated by gel filtration and the enzyme was shown to be significantly protected by the complex formation rom autoinactivation under nonreducing conditions. The stoichiometry of the complex formation was found to be 2 :1 (enzyme : a2M, mol/mol). These results demonstrate the entrapment and concomitant inhibition of HTV proteinase by a2M.