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首页> 外文期刊>The Biochemical Journal >Evaluation of the role of proline residues flanking the RGD motif of dendroaspin, an inhibitor of platelet aggregation and cell adhesion
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Evaluation of the role of proline residues flanking the RGD motif of dendroaspin, an inhibitor of platelet aggregation and cell adhesion

机译：评估脯氨酰胺残基在dendroaspin的RGD基序两侧的作用，dendroaspin是血小板聚集和细胞粘附的抑制剂

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摘要

The effect of a panel of proline mutants of dendroaspin, an inhibitor of platelet aggregation and cell adhesion, including A(42)- dendroaspin, A(17)-dendroaspin, A(49)-dendroaspin, A(42,47)-dendroaspin and A(47,49)-dendroaspin, was investigated using platelet-aggregation and cell-adhesion assays. Here we show that a single alanine-for-proline substitution did not affect potency when measured as the ability either to inhibit platelet aggregation induced by ADP (IC50 approximate to 170 nM) or to block transfected A375-SM cell adhesion to fibrinogen in the presence of Mn2+ as compared with wild-type dendroaspin. By comparison, double proline substitution with alanines significantly reduced the potency in both assays by approx. 5-8-fold. These observations, therefore, suggest that proline residues flanking the RGD motif in dendroaspin and other RGD-containing venom proteins, e.g. disintegrins, may contribute to maintaining a favourable conformation for the solvent-exposed RGD site for its recognition by integrin receptors. [References: 41]
机译：一组dendroaspin脯氨酸突变体的作用，dendroaspin是血小板聚集和细胞粘附的抑制剂，包括A（42）-dendroaspin，A（17）-dendroaspin，A（49）-dendroaspin，A（42,47）-dendroaspin和A（47,49）-dendroaspin，使用血小板聚集和细胞粘附试验进行了研究。在这里，我们显示了单个丙氨酸对脯氨酸的取代不会影响效力，因为它具有抑制ADP诱导的血小板凝集（IC50约为170 nM）或阻止转染的A375-SM细胞粘附到纤维蛋白原的能力。 Mn2 +与野生型树状蛇毒素相比。相比之下，用丙氨酸双脯氨酸取代可显着降低两种测定的效价。 5-8倍。因此，这些观察结果表明，在树突状毒素和其他含RGD的毒蛋白例如RGC中，RGD基序侧翼的脯氨酸残基。 Disintegrins，可能有助于为溶剂暴露的RGD位点保持良好的构象，以使其被整联蛋白受体识别。 [参考：41]

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