Vajragupta Opa, Boonchoong Preecha, Morris Garrett M, Olson Arthur J
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Mahidol University, 447 Sri-Ayudhya Road, Bangkok 10400, Thailand.
Bioorg Med Chem Lett. 2005 Jul 15;15(14):3364-8. doi: 10.1016/j.bmcl.2005.05.032.
Structure models for the interaction of curcumin with HIV-1 integrase (IN) and protease (PR) were investigated using computational docking. Curcumin was found to bind preferentially in similar ways to the active sites of both IN and PR. For IN, the binding site is formed by residues Asp64, His67, Thr66, Glu92, Thr93, Asp116, Ser119, Asn120, and Lys159. Docked curcumin contacts the catalytic residues adjacent to Asp116 and Asp64, and near the divalent metal (Mg2+). In the PR docking, the curcumin structure fitted well to the active site, interacting with residues Asp25, Asp29, Asp30, Gly27', Asp29', and Asp30'. The results suggest that o-hydroxyl and/or keto-enol structures are important for both IN and PR inhibitory actions. The symmetrical structure of curcumin seems to play an important role for binding to the PR protein, whereas the keto-enol and only one side of the terminal o-hydroxyl showed tight binding to the IN active site.
利用计算对接研究了姜黄素与HIV-1整合酶（IN）和蛋白酶（PR）相互作用的结构模型。发现姜黄素以相似的方式优先结合于IN和PR的活性位点。对于IN，结合位点由天冬氨酸64、组氨酸67、苏氨酸66、谷氨酸92、苏氨酸93、天冬氨酸116、丝氨酸119、天冬酰胺120和赖氨酸159的残基形成。对接的姜黄素与天冬氨酸116和天冬氨酸64附近以及二价金属（Mg2+）附近的催化残基接触。在PR对接中，姜黄素结构与活性位点拟合良好，与天冬氨酸25、天冬氨酸29、天冬氨酸30、甘氨酸27'、天冬氨酸29'和天冬氨酸30'的残基相互作用。结果表明，邻羟基和/或酮-烯醇结构对于IN和PR的抑制作用都很重要。姜黄素的对称结构似乎在与PR蛋白的结合中起重要作用，而酮-烯醇和末端邻羟基的一侧与IN活性位点紧密结合。
