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More recently, CQ is also becoming recognized as an important therapeutic compound for the treatment of autoimmune disorders and has shown activity as an anticancer agent. However, the full extent of CQ pharmacology in humans is still unclear. Herein, we demonstrate that the lysosomal protein saposin\u2005B (sapB), critical for select lipid degradation, binds CQ with implications for both CQ function and toxicity. Using isothermal titration calorimetry (ITC) and fluorescence quenching experiments, CQ was shown to bind to the dimeric form of sapB at both pH\u20055.5 and pH\u20057.4 with an average binding affinity of 2.3\u00d710<jats:sup>4<\/jats:sup>\u2009<jats:sc>m<\/jats:sc><jats:sup>\u22121<\/jats:sup>. X\u2010ray crystallography confirmed this, and the first complete crystal structure of sapB with a bound small molecule (CQ) is reported. The results suggest that sapB might play a role in mitigating CQ\u2010based toxicity and that sapB might itself be overwhelmed by CQ causing impaired lipid degradation.<\/jats:p>","DOI":"10.1002\/cmdc.201500494","type":"journal-article","created":{"date-parts":[[2015,11,30]],"date-time":"2015-11-30T05:39:41Z","timestamp":1448861981000},"page":"277-282","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["The Lysosomal Protein Saposin\u2005B Binds Chloroquine"],"prefix":"10.1002","volume":"11","author":[{"given":"Brian P.","family":"Huta","sequence":"first","affiliation":[{"name":"Department of Chemistry Syracuse University  111 College Place Syracuse NY 13244 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matthew R.","family":"Mehlenbacher","sequence":"additional","affiliation":[{"name":"Department of Chemistry State University of New York at Potsdam  Potsdam NY 13676 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yan","family":"Nie","sequence":"additional","affiliation":[{"name":"Department of Chemistry Syracuse University  111 College Place Syracuse NY 13244 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xuelei","family":"Lai","sequence":"additional","affiliation":[{"name":"European Synchrotron Radiation Facility  Grenoble 38054 France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chloe","family":"Zubieta","sequence":"additional","affiliation":[{"name":"Laboratoire de Physiologie Cellulaire &amp; V\u00e9g\u00e9tale iRTSV, UMR 5168 CNRS\/CEA\/INRA\/Univ. Grenoble Alpes  Grenoble 38054 France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fadi","family":"Bou\u2010Abdallah","sequence":"additional","affiliation":[{"name":"Department of Chemistry State University of New York at Potsdam  Potsdam NY 13676 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert P.","family":"Doyle","sequence":"additional","affiliation":[{"name":"Department of Chemistry Syracuse University  111 College Place Syracuse NY 13244 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2015,11,30]]},"reference":[{"key":"e_1_2_2_1_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00436-012-2886-x"},{"key":"e_1_2_2_2_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.307.6895.49"},{"key":"e_1_2_2_3_1","first-page":"415","volume":"12","author":"Bernstein H. N.","year":"1967","journal-title":"Surv. 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