Active-site mobility in human immunodeficiency virus, type 1, protease as demonstrated by crystal structure of A28S mutant.
Active-site mobility in human immunodeficiency virus, type 1, protease as demonstrated by crystal structure of A28S mutant.
复制标题
A28S 突变体的晶体结构证明了 1 型人类免疫缺陷病毒蛋白酶的活性位点移动性。
DOI：
10.1002/pro.5560070209
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发表时间：
1998
期刊：
影响因子：
--
通讯作者：
Tang,J
中科院分区：
文献类型：
--
作者：
Hong,L;Hartsuck,JA;Foundling,S;Ermolieff,J;Tang,J
The mutation Ala28to serine in human immunodeficiency virus, type 1, (HIV‐1) protease introduces putative hydrogen bonds to each active‐site carboxyl group. These hydrogen bonds are ubiquitous in pepsin‐like eukaryotic aspartic proteases. In order to understand the significance of this difference between HIV‐1 protease and homologous, eukaryotic aspartic proteases, we solved the three‐dimensional structure of A28S mutant HIV‐1 protease in complex with a peptidic inhibitor U‐89360E. The structure has been determined to 2.0 Å resolution with an R factor of 0.194. Comparison of the mutant enzyme structure with that of the wild‐type HIV‐1 protease bound to the same inhibitor (Hong L, Treharne A, Hartsuck JA, Foundling S, Tang J, 1996,Biochemistry 35:10627‐10633) revealed double occupancy for the Ser28hydroxyl group, which forms a hydrogen bond either to one of the oxygen atoms of the active‐site carboxyl or to the carbonyl oxygen of Asp30. We also observed marked changes in orientation of the Asp25catalytic carboxyl groups, presumably caused by the new hydrogen bonds. These observations suggest that catalytic aspartyl groups of HIV‐1 protease have significant conformational flexibility unseen in eukaryotic aspartic proteases. This difference may provide an explanation for some unique catalytic properties of HIV‐1 protease.
