Exploring the Multiligand Binding Specificity of Saposin B Reveals Two Binding Sites,ACS Omega

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Exploring the Multiligand Binding Specificity of Saposin B Reveals Two Binding Sites
ACS Omega ( IF 3.7 ) Pub Date : 2017-10-26 00:00:00 , DOI: 10.1021/acsomega.7b01334
Jay Tinklepaugh ₁ , Britannia M. Smith ₂ , Etta Hanlon ₁ , Chloe Zubieta ₃ , Fadi Bou-Abdallah ₂ , Robert P. Doyle _{1,

4}

Affiliation

Saposin B (SapB) is a human lysosomal protein, critical for the degradation of O-sulfogalactosylceramide (sulfatide). SapB binds sulfatide and presents it to the active site of the enzyme arylsulfatase A. Deficiency of SapB leads to fatal activator-deficient metachromatic leukodystrophy. Given the conformational flexibility and the large hydrophobic “pocket” produced upon (physiologically relevant) homodimerization, SapB may have broader substrate diversity than originally thought. Herein, we present evidence using fluorescence spectroscopy and computational docking studies that SapB binds a wide variety of ligands at K_D values varying from micromolar to nanomolar, with entropy being the primary driving force. We further demonstrate, for the first time, that SapB has two binding sites that can sequentially (and in a preferred order) accommodate up to two ligands at once.

中文翻译：

探索Saposin B的多配体结合特异性揭示了两个结合位点。

Saposin B（SapB）是一种人类溶酶体蛋白，对O-磺基半乳糖基神经酰胺（硫化物）的降解至关重要。SapB结合硫化物并将其呈递给芳基硫酸酯酶A的活性位点。SapB的缺乏会导致致命的活化剂缺陷型变色性白细胞营养不良。鉴于构象柔韧性和（生理上相关的）均二聚作用产生的较大的疏水性“口袋”，SapB的底物多样性可能比最初的想象的要广。在这里，我们提供了使用荧光光谱和计算机对接研究的证据，表明SapB在K _D结合了多种配体值从微摩尔到纳摩尔不等，熵是主要驱动力。我们进一步首次证明了SapB具有两个结合位点，它们可以顺序地（以优选的顺序）一次容纳多达两个配体。

更新日期：2017-10-26

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