ACTIVITY OF LINKED HIV-1 PROTEINASE DIMERS CONTAINING MUTATIONS IN THE ACTIVE-SITE REGION

Mutations were introduced into the active site triplet (Asp-Thr-Gly) o f one or both subunits of a linked dimer of human immunodeficiency vir us type 1 proteinase. Mutation of Thr to Ser in one or both subunits d id not alter the activity of the enzyme substantially, whereas its mut ation to Asn in one subunit caused a dramatic decrease in catalytic ef ficiency. Mutation of Gly to Val one subunit also yielded an enzyme wi th very low activity. The enzymes containing Thr --> Asn and Gly --> V al mutations in both subunits resulted in inactive enzymes, based on t heir inability to self-process and on assay with an oligopeptide subst rate. The dramatic decrease in enzyme efficiency of the mutants was in terpreted using molecular models of the enzymes.