Cover Picture: The Lysosomal Protein Saposin B Binds Chloroquine (ChemMedChem 3/2016). Issue 3 (2nd February 2016)

• Record Type: Journal Article
• Authors: Huta, Brian P.; Mehlenbacher, Matthew R.; Nie, Yan; Lai, Xuelei; Zubieta, Chloe; Bou‐Abdallah, Fadi; Doyle, Robert P.
• Is Part Of: ChemMedChem. Volume 11:Issue 3(2016)
• Page Start: 246
• Page End: 246
• Publication Date: 2016-02-02
• Subjects: chloroquine -- isothermal titration calorimetry -- lysosomes -- malaria -- protein crystal structures -- saposin B; Pharmaceutical chemistry -- Periodicals; 615.19005
• DOI: 10.1002/cmdc.201600030
• Languages: English
• ISSNs: 1860-7179

Abstract

Abstract : The front cover picture shows the binding of the antimalarial drug chloroquine by the lysosomal protein saposin B. Chloroquine is a lysosomotropic drug with toxicity associated with prolonged use. The implication of binding by saposin B (as confirmed by isothermal titration calorimetry, fluorescence spectroscopy, and protein crystallography) is the possible decrease or impairment of lysosomal lipid hydrolysis normally facilitated by saposin B. Overall, this work opens a new direction in understanding chloroquine′s complicated pharmacological safety and demonstrates a new class of substrates for saposin B, while also providing the first protein crystal structure of saposin B with a bound substate. More information can be found in the Communication by Robert P. Doyle, Fadi Bou‐Abdallah, Chloe Zubieta et al. onpage 277 in Issue 3, 2016 (DOI:10.1002/cmdc.201500494 ).