MUTANT HIV-1 PROTEINASE WITH A MODIFIED ACTIVE-SITE REGION

Comparative analysis of known three-dimensional structures of the aspa rtic proteases of higher organisms has revealed a conserved group of a mino acid residues which, although separated in the polypeptide sequen ce, form a continuous hydrogen bond network involving essential carbox yls. The role of this group of residues was evaluated by engineering i t into human immunodeficiency virus protease, which lacks it. To this goal, five mutations and two deletions were carried out. The variant e nzyme was nearly as active as the original one but exhibited markedly altered specificity and pH optimum. The results explain the structural bases of such changes. The mutated residues include those responsible for virus resistance against protease inhibitors of therapeutic value .