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Exploring the Multiligand Binding Specificity of Saposin B Reveals Two Binding Sites.

ABSTRACT: 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 KD 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.

SUBMITTER: Tinklepaugh J

PROVIDER: S-EPMC5664142 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature

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Exploring the Multiligand Binding Specificity of Saposin B Reveals Two Binding Sites.

Tinklepaugh Jay J Smith Britannia M BM Hanlon Etta E Zubieta Chloe C Bou-Abdallah Fadi F Doyle Robert P RP

ACS omega 20171026 10

Saposin B (SapB) is a human lysosomal protein, critical for the degradation of <i>O</i>-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 ...[more]

PMID: 29104953

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