Gustchina A, Weber I T
Macromolecular Structure Laboratory, NCI Frederick Cancer Research and Development Center, Frederick, Maryland 21702.
Proteins. 1991;10(4):325-39. doi: 10.1002/prot.340100406.
The different isolates available for HIV-1 and HIV-2 were compared for the region of the protease (PR) sequence, and the variations in amino acids were analyzed with respect to the crystal structure of HIV-1 PR with inhibitor. Based on the extensive homology (39 identical out of 99 residues), models were built of the HIV-2 PR complexed with two different aspartic protease inhibitors, acetylpepstatin and a renin inhibitor, H-261. Comparison of the HIV-1 PR crystal structure and the HIV-2 PR model structure and the analysis of the changes found in different isolates showed that correlated substitutions occur in the hydrophobic interior of the molecule and at surface residues involved in ionic or hydrogen bond interactions. The substrate binding residues of HIV-1 and HIV-2 PRs show conservative substitutions of four residues. The difference in affinity of HIV-1 and HIV-2 PRs for the two inhibitors appears to be due in part to the change of Val 32 in HIV-1 PR to Ile in HIV-2 PR.
对可获得的不同HIV-1和HIV-2分离株的蛋白酶（PR）序列区域进行了比较，并针对与抑制剂结合的HIV-1 PR晶体结构分析了氨基酸变异情况。基于广泛的同源性（99个残基中有39个相同），构建了与两种不同天冬氨酸蛋白酶抑制剂（乙酰胃蛋白酶抑制剂和一种肾素抑制剂H-261）复合的HIV-2 PR模型。HIV-1 PR晶体结构与HIV-2 PR模型结构的比较以及对不同分离株中发现的变化的分析表明，相关替代发生在分子的疏水内部以及参与离子或氢键相互作用的表面残基处。HIV-1和HIV-2 PR的底物结合残基显示出四个残基的保守替代。HIV-1和HIV-2 PR对这两种抑制剂亲和力的差异似乎部分归因于HIV-1 PR中的缬氨酸32变为HIV-2 PR中的异亮氨酸。
