Czub Mateusz P, Venkataramany Barat S, Majorek Karolina A, Handing Katarzyna B, Porebski Przemyslaw J, Beeram Sandya R, Suh Kyungah, Woolfork Ashley G, Hage David S, Shabalin Ivan G, Minor Wladek
Department of Molecular Physiology and Biological Physics , University of Virginia , 1340 Jefferson Park Avenue , Charlottesville , VA 22908 , USA . Email:
Center for Structural Genomics of Infectious Diseases (CSGID) , University of Virginia , 1340 Jefferson Park Avenue , Charlottesville , VA 22908 , USA.
Chem Sci. 2018 Dec 17;10(6):1607-1618. doi: 10.1039/c8sc04397c. eCollection 2019 Feb 14.
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.
血清白蛋白是哺乳动物血浆中含量最丰富的蛋白质，负责运输金属、药物以及包括激素在内的各种代谢物。我们报道了首个与主要雄性性激素睾酮结合的白蛋白结构。睾酮结合在两个位点，这两个位点均不与先前提出的Sudlow位点I重叠。我们通过两种不同方法测定了睾酮与马和人白蛋白的结合常数：色氨酸荧光猝灭法和超快亲和萃取法。结合研究以及血清白蛋白上构成结合位点的残基之间的相似性表明，睾酮在两种蛋白质上结合于相同位点。我们对白蛋白与激素、药物及其他生物相关化合物复合物的比较分析强烈表明，血液中存在的多种化合物与血清白蛋白介导的睾酮运输之间存在干扰。我们讨论了我们的研究结果与在人类患者中观察到的一些现象之间可能存在的联系，例如糖尿病患者睾酮水平较低。
