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首页> 外文期刊>Biochemistry >Inhibition of the human sodium/bile acid cotransporters by side-specific methanethiosulfonate sulfhydryl reagents: substrate-controlled accessibility of site of inactivation.
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Inhibition of the human sodium/bile acid cotransporters by side-specific methanethiosulfonate sulfhydryl reagents: substrate-controlled accessibility of site of inactivation.

机译:抑制人钠/胆汁酸分解器通过侧面特异性甲烷磺酸磺酸磺酸盐试剂:灭活部位的基材控制可接近性。

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摘要

Mammalian sodium/bile acid cotransporters (SBATs) constitute a subgroup of the sodium cotransporter superfamily and function in the enterohepatic circulation of bile acids. They are glycoproteins with an exoplasmic N-terminus, seven or nine transmembrane segments, and a cytoplasmic C-terminus. They exhibit no significant homology with other members of the sodium cotransporter family and there is limited structure/function information available for the SBATs. Membrane-impermeant methanethiosulfonates (MTS) inhibited bile acid transport by alkylation of cysteine 270 (apical SBAT)/266 (basolateral SBAT) that is fully conserved among the sodium/bile acid cotransporters. The accessibility of this residue to MTS reagent is regulated by the natural substrates, sodium and bile acid. In experiments with the apical SBAT, sodium alone increases the reactivity with the thiol reagents as compared to sodium-free medium. In contrast, bile acids protect the SBATs from inactivation, although only in the presence of sodium. The inhibition and protection data suggest that cysteine 270/266 lies in a sodium-sensitive region of the SBATs that is implicated in bile acid transport.
机译:哺乳动物钠/胆汁酸COTRANSPORTERS(SBATS)构成了胆汁酸钠的亚群和胆汁酸的肠溶血液循环中的亚组。它们是具有外质N-末端,七个或九个跨膜段的糖蛋白,以及细胞质C-末端。它们与COTRANSPORTER家族的其他成员没有显着的同源性,并且可以为SBATS提供有限的结构/功能信息。膜 - 缺乏甲酰基磺酸盐(MTS)通过半胱氨酸270(顶端SBAT)/ 266(基石SBAT)烷基化抑制胆汁酸输送,所述半胱氨酸270(顶端SBAT)/ 266(基石SBAT)在钠/胆汁酸性酸/胆酸盐转发器中完全保守。将该残余物的可及性与MTS试剂进行调节,由天然底物,钠和胆汁酸调节。在具有顶端SBAT的实验中,与无钠培养基相比,单独的单独增加与硫醇试剂的反应性。相比之下,胆汁酸保护SBATS免于失活,但仅在钠存在下。抑制和保护数据表明半胱氨酸270/266位于含有胆汁酸输送的SBAT的钠敏感区域中。

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