Heme impairs allosterically drug binding to human serum albumin Sudlow's site I
Heme impairs allosterically drug binding to human serum albumin Sudlow's site I
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DOI：
10.1016/j.bbrc.2005.06.127
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发表时间：
2005-08-26
影响因子：
3.1
通讯作者：
Fasano, M
中科院分区：
文献类型：
--
作者：
Ascenzi, P;Bocedi, A;Fasano, M
人血清白蛋白（HSA）是血浆中最重要的蛋白质，以其特殊的配体（例如，血红素和药物）结合能力。本文报道了氯磺丙脲、洋地黄毒苷、呋塞米、吲哚美辛、保泰松、磺胺异恶唑和甲苯磺丁脲与HSA和亚铁血红素-HSA的结合。此外，铁血红素结合到HSA的存在和不存在的药物进行了研究。药物与亚铁血红素-HSA的Sudlow位点I结合的缔合平衡常数（范围在1.7 × 10（3）和1.6 × 10（5）M-1之间）比药物与无亚铁血红素的HSA结合的缔合平衡常数（范围在1.9 × 10（4）和1.8 × 10（6）M-1之间）低一个数量级。根据关联函数，血红素与HSA结合的缔合平衡常数值从无药物时的7.8 × 10（7）M-1降低到有药物时的7.0 × 10（6）M-1。这些发现代表了血红素对药物结合HSA Sudlow位点I的变构抑制的明确证据。根据相关功能，药物损害血红素与HSA的变构结合。这些结果似乎与药物治疗和管理有关。(c)2005年爱思唯尔公司All rights reserved.
Human serum albumin (HSA), the most prominent protein in plasma, is best known for its exceptional ligand (e.g., heme and drugs) binding capacity. Here, the binding of chlorpropamide, digitoxin, furosemide, indomethacin, phenylbutazone, sulfisoxazole, and tolbutamide to HSA and ferric heme-HSA is reported. Moreover, ferric heme binding to HSA in the absence and presence of drugs has been investigated. Values of the association equilibrium constant for drug binding to Sudlow's site I of ferric heme-HSA (ranging between 1.7 x 10(3) and 1.6 x 10(5) M-1) are lower by one order of magnitude than those for drug binding to ferric heme-free HSA (ranging between 1.9 X 10(4) and 1.8 x 10(6) M-1). According to linked functions, the value of the association equilibrium constant for heme binding to HSA decreases from 7.8 X 10(7) M-1, in the absence of drugs to 7.0 x 10(6) M-1, in the presence of drugs. These findings represent a clear-cut evidence for the allosteric inhibition of drug binding to HSA Sudlow's site I by the heme. According to linked functions, drugs impair allosterically heme binding to HSA. These results appear to be relevant in the drug therapy and management. (c) 2005 Elsevier Inc. All rights reserved.