Circulatory zinc transport is controlled by distinct interdomain sites on mammalian albumins.
Circulatory zinc transport is controlled by distinct interdomain sites on mammalian albumins.
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DOI：
10.1039/c6sc02267g
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发表时间：
2016-11-01
期刊：
影响因子：
8.4
通讯作者：
Minor W
中科院分区：
文献类型：
--
作者：
Handing KB;Shabalin IG;Kassaar O;Khazaipoul S;Blindauer CA;Stewart AJ;Chruszcz M;Minor W
基本营养锌主要的循环转运是通过其与血清相册的结合，我们在与锌结构中呈现了哺乳动物专辑的第一个晶体结构，以及参与的锌结合数据。
锌是体内必不可少的营养素，这是数百种人类酶的催化活性，实际上是所有生物学过程，因此血清中的稳态和运输是至关重要的。结构允许在这两张专辑中的主要锌结合位点以及较弱的锌结合位点的明确鉴定。HSA和ESA中的主要位点具有四面体的几何形状，并包括三个蛋白质配体，包括His67，His247和His247和Asp249和Asp249和Water Munec的satriant an 7 contriation toce his247和sater and other an his247和satriation。最高亲和力Zn2+位点Zn2+与HSA和ESA的结合提供了具有20-50倍弱的亲和力，在特定的生理条件下可能会变得重要对我们至关重要了解血清白蛋白在循环Zn2+处理和细胞递送中的作用。
Circulatory transport of the essential nutrient zinc primarily occurs through its binding to serum albumin. Here, we present the first crystal structures of mammalian albumins in complex with zinc. These structures, together with accompanying zinc binding data, allow identification of key zinc transport sites on human and equine albumins. Zinc is an essential nutrient in the body; it is required for the catalytic activity of many hundreds of human enzymes and virtually all biological processes, therefore its homeostasis and trafficking is of crucial interest. Serum albumin is the major carrier of Zn2+ in the blood and is required for its systemic distribution. Here we present the first crystal structures of human serum albumin (HSA) and equine serum albumin (ESA) in complex with Zn2+. The structures allow unambiguous identification of the major zinc binding site on these two albumins, as well as several further, weaker zinc binding sites. The major site in both HSA and ESA has tetrahedral geometry and comprises three protein ligands from the sidechains of His67, His247 and Asp249 and a water molecule. Isothermal titration calorimetric studies of a HSA H67A mutant confirm this to be the highest affinity Zn2+ site. Furthermore, analysis of Zn2+ binding to HSA and ESA proved the presence of secondary sites with 20–50-fold weaker affinities, which may become of importance under particular physiological conditions. Both calorimetry and crystallography suggest that ESA possesses an additional site compared to HSA, involving Glu153, His157 and His288. The His157 residue is replaced by Phe in HSA, incapable of metal coordination. Collectively, these findings are critical to our understanding of the role serum albumin plays in circulatory Zn2+ handling and cellular delivery.