PMID: 9450540Feb 5, 1998Paper

Structure of a G48H mutant of HIV-1 protease explains how glycine-48 replacements produce mutants resistant to inhibitor drugs

FEBS Letters
L HongJ Tang

Abstract

The crystal structure of human immunodeficiency virus type 1 (HIV-1) protease mutant G48H with peptidic inhibitor U-89360E is described. Comparison with wild-type protease-inhibitor complex shows that mutation of flap residue 48 to histidine allows stabilizing van der Waals contacts between the side chains of His48 and Phe53 as well as between His48 and the P2' and P3' inhibitor subsites. The flap region is less mobile than in the wild-type enzyme. A model of saquinavir-resistant mutant protease G48V in complex with saquinavir predicts interactions similar to those found in the G48H crystal. Energetic calculations confirm the similarity of the His48 and Val48 interactions.

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Citations

Jan 16, 2002·Protein Science : a Publication of the Protein Society·Nancy M KingCelia A Schiffer
Feb 1, 2012·Bioinformatics·J W HealR A Römer
Aug 16, 2002·Antiviral Chemistry & Chemotherapy·G AhlsénU H Danielson
Jan 24, 2007·Physical Chemistry Chemical Physics : PCCP·Zheng Li, Themis Lazaridis
May 29, 2003·Journal of the American Chemical Society·Zheng Li, Themis Lazaridis
Dec 22, 2007·Chemical Reviews·Philip Ball
Apr 12, 2002·Biochemical and Biophysical Research Communications·Immanuel BlumenzweigMoshe Kotler
Nov 24, 2004·Journal of Chemical Information and Computer Sciences·Miguel X FernandesMichael K Gilson

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