The ABCG2 protein has a key role in the transport of a wide range of structurally dissimilar endo‐ and xenobiotics in the human body, especially in the tissue barriers and the metabolizing or secreting organs. The human ABCG2 gene harbors a high number of polymorphisms and mutations, which may significantly modulate its expression and function. Recent high‐resolution structural data, complemented with molecular dynamic simulations, may significantly help to understand intramolecular movements and substrate handling, as well as the effects of mutations on the membrane transporter function of ABCG2. As reviewed here, structural alterations may result not only in direct alterations in drug binding and transporter activity, but also in improper folding or problems in the carefully regulated process of trafficking, including vesicular transport, endocytosis, recycling, and degradation. Here, we also review the clinical importance of altered ABCG2 expression and function in general drug metabolism, cancer multidrug resistance, and impaired uric acid excretion, leading to gout.

中文翻译：

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ABCG2/BCRP 转运蛋白及其变体——从结构到病理

ABCG2 蛋白在人体中各种结构不同的内源性和外源性物质的运输中起关键作用，尤其是在组织屏障和代谢或分泌器官中。人类 ABCG2 基因具有大量的多态性和突变，这可能会显着调节其表达和功能。最近的高分辨率结构数据，辅以分子动力学模拟，可能有助于理解分子内运动和底物处理，以及突变对 ABCG2 膜转运蛋白功能的影响。如本文所述，结构改变不仅可能导致药物结合和转运蛋白活性的直接改变，还会导致折叠不当或谨慎调节的贩运过程中的问题，包括囊泡运输，内吞、循环和降解。在这里，我们还回顾了 ABCG2 表达和功能改变在一般药物代谢、癌症多药耐药性和尿酸排泄受损，导致痛风中的临床重要性。