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

被引：19

作者：

Hong, L

Zhang, XJ

Foundling, S

Hartsuck, JA

Tang, J

机构：

[1] Oklahoma Med Res Fdn, Prot Studies & Crystallog Programs, Oklahoma City, OK 73104 USA

[2] Univ Oklahoma, Hlth Sci Ctr, Dept Biochem & Mol Biol, Oklahoma City, OK 73190 USA

来源：

FEBS LETTERS | 1997年 / 420卷 / 01期

关键词：

HIV protease; mutation; saquinavir; drug resistance;

D O I：

10.1016/S0014-5793(97)01477-4

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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 His(48) and Phe(53) as well as between His(48) and the P-2' and P-3' 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 His and Val(48) interactions. (C) 1997 Federation of European Biochemical Societies.

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收藏

页码：11 / 16

页数：6

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