Crystal structure of an FIV/HIV chimeric protease complexed with the broad-based inhibitor, TL-3

摘要: We have obtained the 1.7 A crystal structure of FIV protease (PR) in which 12 critical residues around active site been substituted with structurally equivalent HIV PR (12X PR). The chimeric was crystallized complex broad-based inhibitor TL-3, inhibits wild type and PRs, as well 12X several drug-resistant mutants [1–4]. Biochemical analyses demonstrated that TL-3 these PRs order > PR, Ki values 1.5 nM, 10 41 respectively [2–4]. Comparison structures complexes wild-typeFIV revealed theformation additinal van der Waals interactions between enzyme mutant PR. retained hydrogen bonding flap regions involving comparison to both However, more closely resemble those having gained stabilizing intra-flap not present These findings offer a structural explanation for observed inhibitor/substrate binding properties