Structure of a G48H mutant of HIV-1 protease explains how glycine-48 replacements produce mutants resistant to inhibitor drugs.
Structure of a G48H mutant of HIV-1 protease explains how glycine-48 replacements produce mutants resistant to inhibitor drugs.
复制标题
HIV-1 蛋白酶 G48H 突变体的结构解释了甘氨酸 48 替代物如何产生对抑制剂药物具有抗性的突变体。
DOI：
10.1016/s0014-5793(97)01477-4
复制
发表时间：
1997
期刊：
影响因子：
3.5
通讯作者：
Tang,J
中科院分区：
文献类型：
--
作者：
Hong,L;Zhang,XJ;Foundling,S;Hartsuck,JA;Tang,J
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 His48and Phe53as well as between His48and 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 His48and Val48interactions.
