首页> 外文期刊>European Journal of Medicinal Chemistry: Chimie Therapeutique >A molecular model of a putative substrate releasing conformation of multidrug resistance protein 5 (MRP5).
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A molecular model of a putative substrate releasing conformation of multidrug resistance protein 5 (MRP5).

机译:假定的底物释放多重耐药蛋白5(MRP5)构象的分子模型。

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摘要

The ATP-binding cassette (ABC) transporter multidrug resistance protein 5 (MRP5) contributes to the cellular export of organic anions, including guanosine 3'-5' cyclic monophosphate (cGMP). The structural knowledge of this protein is limited, and in lack of an MRP5 X-ray structure, a model of MRP5 was constructed based on the homology with the bacterial ABC transporter Sav1866 from Staphylococcus aureus, which has been crystallised in an outward-facing, substrate releasing conformation. Two putative binding sites were identified, and docking of cGMP indicated that TMHs 1-3, 6, 11 and 12 were in contact with the ligands in binding site 1, while TMHs 1, 3, 5-8 were in contact with the ligands in binding site 2. The proposed MRP5 model may be used for further experimental studies of the molecular structure and function of this member of the ABC-transporter superfamily.
机译:ATP结合盒(ABC)转运蛋白多药耐药蛋白5(MRP5)有助于细胞内有机阴离子的输出,包括鸟苷3'-5'环一磷酸(cGMP)。该蛋白质的结构知识有限,并且缺乏MRP5 X射线结构,因此基于与金黄色葡萄球菌的细菌ABC转运蛋白Sav1866的同源性构建了MRP5模型,该模型已在向外结晶,底物释放构象。鉴定出两个推定的结合位点,cGMP的对接表明TMH 1-3、6、11和12与结合位点1的配体接触,而TMH 1、3、5-8则与结合位点1的配体接触。结合位点2。提出的MRP5模型可用于ABC转运蛋白超家族这一成员的分子结构和功能的进一步实验研究。

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