Exploring the multiligand binding specificity of saposin B reveals two binding sites

Jay Tinklepaugh, Britannia M. Smith, Etta Hanlon, Chloe Zubieta, Fadi Bou-Abdallah, Robert P. Doyle

Research output: Contribution to journalArticlepeer-review

4 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)7141-7145
Number of pages5
JournalACS Omega
Issue number10
StatePublished - Oct 31 2017

ASJC Scopus subject areas

  • General Chemistry
  • General Chemical Engineering


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