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首页> 外文期刊>The FEBS journal >Allosteric modulation of anti-HIV drug and ferric heme binding to human serum albumin
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Allosteric modulation of anti-HIV drug and ferric heme binding to human serum albumin

机译：抗HIV药物和铁血红素与人血清白蛋白结合的变构调节

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Human serum albumin (HSA), the most prominent protein in plasma, is best known for its exceptional capacity to bind ligands (e.g. heme and drugs). Here, binding of the anti-HIV drugs abacavir, atazanavir, didanosine, efavirenz, emtricitabine, lamivudine, nelfinavir, nevirapine, ritonavir, saquinavir, stavudine, and zidovudine to HSA and ferric heme-HSA is reported. Ferric heme binding to HSA in the absence and presence of anti-HIV drugs was also investigated. The association equilibrium constant and second-order rate constant for the binding of anti-HIV drugs to Sudlow's site I of ferric heme-HSA are lower by one order of magnitude than those for the binding of anti-HIV drugs to HSA. Accordingly, the association equilibrium constant and the second-order rate constant for heme binding to HSA are decreased by one order of magnitude in the presence of anti-HIV drugs. In contrast, the first-order rate constant for ligand dissociation from HSA is insensitive to anti-HIV drugs and ferric heme. These findings represent clear-cut evidence for the allosteric inhibition of anti-HIV drug binding to HSA by the heme. In turn, anti-HIV drugs allosterically impair heme binding to HSA. Therefore, Sudlow's site I and the heme cleft must be functionally linked.
机译：人血浆白蛋白（HSA）是血浆中最突出的蛋白质，以其与配体（例如血红素和药物）结合的超强能力而闻名。在此，报道了抗HIV药物阿巴卡韦，阿扎那韦，二达肌苷，依非韦伦，恩曲他滨，拉米夫定，奈非那韦，奈韦拉平，利托那韦，沙奎那韦，司他夫定和齐多夫定与HSA和铁血红素-HSA的结合。还研究了在不存在和存在抗HIV药物的情况下铁血红素与HSA的结合。抗HIV药物与铁血红素-HSA的Sudlow位点I结合的缔合平衡常数和二级速率常数比抗HIV药物与HSA的结合缔合平衡常数和二级速率常数低一个数量级。因此，在抗HIV药物的存在下，血红素与HSA结合的缔合平衡常数和二级速率常数降低了一个数量级。相反，配体从HSA上解离的一级速率常数对抗HIV药物和铁血红素不敏感。这些发现代表了血红素对变体抑制抗HIV药物与HSA结合的明确证据。反过来，抗HIV药物会变构破坏血红素与HSA的结合。因此，Sudlow的位点I和血红素裂必须在功能上关联。

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