Critical Domains within the Sequence of Human Organic Anion Transporting Polypeptides
Critical Domains within the Sequence of Human Organic Anion Transporting Polypeptides
复制标题
人类有机阴离子转运多肽序列内的关键结构域。
DOI：
10.2174/1389200214666131229111118
复制
发表时间：
2014-03-01
影响因子：
2.3
通讯作者：
Hong, Mei
中科院分区：
文献类型：
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作者：
Hong, Mei
有机阴离子转运多肽(人OATPs；其他物种OATPs；SLC21/SLCO基因家族)在药物吸收和分布中起着重要作用。近些年来，人们已经获得了大量关于OATP运输底物的信息。基于计算机的水病分析预测，OATP家族成员具有几个结构特征，包括12个跨膜结构域(TM)、细胞外环5处保守的半胱氨酸残基、糖基化位点、PDZ结合结构域以及可能的磷酸化位点。对跨膜区的研究已经确定了几种氨基酸是底物摄取所必需的；而保守的半胱氨酸残基和糖基化位点的突变导致了转运蛋白的错误处理。另一方面，与PDZ蛋白的相互作用和OATPs的磷酸化修饰主要调节这些转运蛋白的运输。虽然在揭示OATP的关键领域方面取得了进展，但信息仍然有限，需要对这些方面进行更多的研究。更好地理解OATP的重要结构域将有助于未来的靶向药物设计和更深入地分析药物处置的个体间差异。
Organic anion-transporting polypeptides (human OATPs; other species Oatps; gene family SLC21/SLCO) play important roles in drug absorption and distribution. In recent years, much information has been obtained on substrates that are transported by OATPs. Computer-based hydropathy analysis predicts that OATP family members share several structural features including twelve transmembrane domains (TMs), conserved cysteine residues at extracellular loop 5, glycosylation sites, PDZ binding domains as well as putative phosphorylation sites. Studies on transmembrane domains have identified several amino acids that are essential for substrate uptake; while mutation of the conserved cysteine residues and glycosylation sites resulted in mis-processing transporter proteins. The interaction with PDZ proteins and phosphorylation modification of OATPs, on the other hand, mainly regulate the trafficking of these transporters. Although progress has been made on revealing the critical domains of OATPs, information is still limited and more studies on these aspects are needed. A better understanding of the important structural domains of OATPs will shed light on future targeted drug design and a more in-depth analysis of inter-individual variability of drug disposition.