Characterization of the Co2+ and Ni2+ binding amino-acid residues of the N-terminus of human albumin -: An insight into the mechanism of a new assay for myocardial ischemia
Characterization of the Co2+ and Ni2+ binding amino-acid residues of the N-terminus of human albumin -: An insight into the mechanism of a new assay for myocardial ischemia
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DOI：
10.1046/j.1432-1327.2001.01846.x
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发表时间：
2001-01-01
期刊：
影响因子：
--
通讯作者：
Lau, E
中科院分区：
文献类型：
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作者：
Bar-Or, D;Curtis, G;Lau, E
据报道，心肌缺血患者在体外表现出外源性Co2+与人血清白蛋白（HSA） n端结合减少。我们研究的目的是模拟HSA的n端变化，这可能解释了这些缺血诱导的钴结合位点的修饰。HPLC、LC-MS和H-1 NMR分析表明，HSA Asp-Ala-His-Lys的n端与过渡金属Co2+和Ni2+结合。合成具有HSA序列前2-12个氨基酸的肽表明，前3个氨基酸Asp-Ala-His对钴的强结合至关重要。通过n -乙酰化修饰HSA的n端肽或删除一个或多个氨基酸导致钴不结合。由于HSA的易感过渡金属结合位点的降解可能是在缺血事件中观察到的钴结合减少的原因，因此检测这种结合减少的分析可能对缺血的诊断有用。
Patients suffering from myocardial ischemia reportedly exhibit reduced in vitro binding of exogenous Co2+ to the N-terminal of human serum albumin (HSA). The purpose of our investigation was to simulate changes in the N-terminus of HSA that may account for these ischemia-induced modifications to the cobalt binding site. HPLC, LC-MS and H-1 NMR analyses have shown that the N-terminal region of HSA Asp-Ala-His-Lys binds the transition metals Co2+ and Ni2+. Synthetic peptides with the first 2-12 amino acids of the HSA sequence demonstrated that the first three amino acids, Asp-Ala-His, are essential for strong binding of cobalt. Modification of the N-terminus peptide of HSA by way of N-acetylation or the deletion of one or more amino acid resulted in no binding of cobalt. Because the degradation of the susceptible, specific transition metal binding site of HSA may account for the decreased cobalt binding observed during ischemic events, an assay that detects this reduced binding could be useful in the diagnosis of ischemia.