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首页> 外文期刊>Infection and immunity >Influence of a glycine or proline substitution on the functional properties of a 14-amino-acid analog of Escherichia coli heat-stable enterotoxin.
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Influence of a glycine or proline substitution on the functional properties of a 14-amino-acid analog of Escherichia coli heat-stable enterotoxin.

机译：甘氨酸或脯氨酸取代对大肠杆菌热稳定肠毒素的14个氨基酸类似物的功能特性的影响。

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Analogs of Escherichia coli heat-stable enterotoxin (ST) differing in chain length or the presence of turn-forming residues were assessed for binding to receptors, activation of particulate guanylate cyclase, and stimulation of secretion in suckling mice. These analogs included the native 18-amino-acid peptide (ST), the 14-amino-acid carboxy terminus of this native peptide with a proline at position 12 (ST[5-18]proline), and the 14-amino-acid carboxy terminus in which the proline at position 12 was substituted with glycine (ST[5-18]glycine). Each analog bound to the receptor in a dose-dependent fashion, completely displacing [125I]ST in competitive binding assays. However, their potencies differed significantly: ST demonstrated the highest affinity (inhibition constant [Ki], 10(-9) M), followed by ST[5-18]proline (Ki, 10(-7) M) and ST[5-18]glycine (Ki, 10(-6) M). Similarly, these peptides maximally activated particulate guanylate cyclase and stimulated intestinal secretion in suckling mice. Their rank order of potency in these assays was similar to that described for receptor binding: ST greater than ST[5-18]proline greater than ST[5-18]glycine. These data demonstrate that the full peptide structure is not absolutely required for pharmacological, biochemical, or biological activity. However, the four amino-terminal residues contribute significantly to the potency of these peptides. In addition, the turn imposed by the proline residue at position 12 is not absolutely required for receptor occupancy or activation of the biochemical cascade that results in intestinal secretion. However, it significantly increases the potency of the toxin. These data illustrate the importance of primary and secondary structures to the biochemical, pharmacological, and physiological activities of the ST produced by E. coli.
机译：评估了链长度不同或存在转弯残基的大肠杆菌热稳定肠毒素（ST）的类似物与受体的结合，颗粒鸟苷酸环化酶的活化以及乳鼠分泌的刺激。这些类似物包括天然的18个氨基酸的肽（ST），该天然肽的14个氨基酸的羧基末端和12位脯氨酸（ST [5-18]脯氨酸），以及14个氨基酸羧基末端，其中第12位的脯氨酸被甘氨酸（ST [5-18]甘氨酸）取代。每个类似物均以剂量依赖性方式与受体结合，在竞争性结合试验中完全取代[125I] ST。但是，它们的效价差异很大：ST表现出最高的亲和力（抑制常数[Ki]，10（-9）M），其次是ST [5-18]脯氨酸（Ki，10（-7）M）和ST [5 -18]甘氨酸（Ki，10（-6）M）。同样，这些肽在乳鼠中最大程度地激活了鸟苷酸环化酶颗粒并刺激了肠道分泌。在这些测定中，它们的效价等级顺序类似于受体结合所描述的：ST大于ST [5-18]脯氨酸，大于ST [5-18]甘氨酸。这些数据表明，药理，生化或生物学活性并非绝对需要完整的肽结构。然而，四个氨基末端残基对这些肽的效力有显着贡献。另外，对于受体占据或激活导致肠道分泌的生化级联反应，并非绝对需要由位置12的脯氨酸残基施加的转角。但是，它显着增加了毒素的效力。这些数据说明一级和二级结构对大肠杆菌产生的ST的生化，药理和生理活性的重要性。

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