L. Hong et al., STRUCTURE OF A G48H MUTANT OF HIV-1 PROTEASE EXPLAINS HOW GLYCINE-48 REPLACEMENTS PRODUCE MUTANTS RESISTANT TO INHIBITOR DRUGS, FEBS letters, 420(1), 1997, pp. 11-16
The crystal structure of human immunodeficiency virus type 1 (HIV-1) p
rotease mutant G48H with peptidic inhibitor U-89360E is described. Com
parison with wild-type protease-inhibitor complex shows that mutation
of flap residue 48 to histidine allows stabilizing van der Waals conta
cts between the side chains of His(48) and Phe(53) as well as between
His(48) and the P-2' and P-3' inhibitor subsites, The flap region is l
ess mobile than in the wild-type enzyme. A model of saquinavir-resista
nt mutant protease G48V in complex with saquinavir predicts interactio
ns similar to those found in the G48H crystal. Energetic calculations
confirm the similarity of the His and Val(48) interactions. (C) 1997 F
ederation of European Biochemical Societies.