Testosterone meets albumin - the molecular mechanism of sex hormone transport by serum albumins
Testosterone meets albumin - the molecular mechanism of sex hormone transport by serum albumins
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DOI：
10.1039/c8sc04397c
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发表时间：
2019-02-14
期刊：
影响因子：
8.4
通讯作者：
Minor, Wladek
中科院分区：
文献类型：
--
作者：
Czub, Mateusz P.;Venkataramany, Barat S.;Minor, Wladek
血清白蛋白是哺乳动物血浆中含量最丰富的蛋白质，负责金属、药物和包括激素在内的各种代谢物的运输。我们报道了第一个白蛋白结构与睾酮，主要的男性性激素的复合体。睾酮结合在两个位点上，这两个位点都不与先前提出的苏德罗位点I重叠。我们用两种不同的方法测定了睾酮与马和人蛋白的结合常数：色氨酸荧光猝灭法和超快亲和萃取法。结合研究和包含血清蛋白结合位点的残基之间的相似性表明，睾酮与两种蛋白质上的相同位点结合。我们对白蛋白复合体与激素、药物和其他生物相关化合物的比较分析强烈表明，血液中存在的一些化合物与血清白蛋白运输睾酮之间存在干扰。我们讨论了我们的发现与在人类患者中观察到的一些现象之间的可能联系，例如糖尿病患者的睾丸激素水平低下。
Serum albumin is the most abundant protein in mammalian blood plasma and is responsible for the transport of metals, drugs, and various metabolites, including hormones. We report the first albumin structure in complex with testosterone, the primary male sex hormone. Testosterone is bound in two sites, neither of which overlaps with the previously suggested Sudlow site I. We determined the binding constant of testosterone to equine and human albumins by two different methods: tryptophan fluorescence quenching and ultrafast affinity extraction. The binding studies and similarities between residues comprising the binding sites on serum albumins suggest that testosterone binds to the same sites on both proteins. Our comparative analysis of albumin complexes with hormones, drugs, and other biologically relevant compounds strongly suggests interference between a number of compounds present in blood and testosterone transport by serum albumin. We discuss a possible link between our findings and some phenomena observed in human patients, such as low testosterone levels in diabetic patients.