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Crystallographic analysis reveals common modes of binding of medium and long-chain fatty acids to human serum albumin

机译:晶体学分析揭示中链和长链脂肪酸与人血清白蛋白结合的常见模式

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Human serum albumin (HSA) is an abundant plasma protein that is responsible for the transport of fatty acids. HSA also binds and perturbs the pharmacokinetics of a wide range of drug compounds. Binding studies have revealed significant interactions between fatty acid and drug-binding sites on albumin but high-resolution structural information on ligand binding to the protein has been lacking. We report here a crystallographic study of five HSA-fatty acid complexes formed using saturated medium-chain and long-chain fatty acids (C10:0, C12:0,C14:0, C16:0 and C18:0). A total of seven binding sites that are occupied by all medium-chain and long-chain fatty acids have been identified, although medium-chain fatty acids are found to bind at additional sites on the protein, yielding a total of 11 distinct binding locations. Comparison of the different complexes reveals key similarities and significant differences in the modes of binding, and serves to rationalise much of the biochemical data on fatty acid interactions with albumin. The two principal drug-binding sites, in sub-domains IIA and IIIA, are observed to be occupied by fatty acids and one of them (in IIIA) appears to coincide with a high-affinity long-chain fatty acid binding site. (C) 2000 Academic Press. [References: 57]
机译:人血清白蛋白(HSA)是一种丰富的血浆蛋白,负责脂肪酸的运输。 HSA还结合并扰乱多种药物化合物的药代动力学。结合研究表明,脂肪酸与白蛋白上的药物结合位点之间存在显着的相互作用,但缺乏有关配体与蛋白质结合的高分辨率结构信息。我们在这里报告了使用饱和的中链和长链脂肪酸(C10:0,C12:0,C14:0,C16:0和C18:0)形成的5种HSA-脂肪酸复合物的晶体学研究。尽管发现中链脂肪酸在蛋白质的其他位点结合,总共产生了11个不同的结合位点,但已鉴定出总共7个被所有中链和长链脂肪酸占据的结合位点。不同复合物的比较揭示了结合方式的关键相似性和显着差异,并有助于理化许多脂肪酸与白蛋白相互作用的生化数据。观察到子域IIA和IIIA中的两个主要药物结合位点被脂肪酸占据,其中一个(在IIIA中)似乎与高亲和力的长链脂肪酸结合位点重合。 (C)2000学术出版社。 [参考:57]

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