Exploration of the Binding Behavior and Function of Saposin B

Date of Award

August 2018

Degree Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Chemistry

Advisor(s)

Robert P. Doyle

Subject Categories

Physical Sciences and Mathematics

Abstract

This thesis seeks to address the binding behavior and functionality of the lysosomal sphingolipid activator protein saposin B (sapB). SapB is critical for the degradation of O-sulfogalactosylceramide by arylsulfatase A and deficiency of sapB leads to a variant form of the fatal lysosomal storage disease Metachromatic leukodystrophy. Discussed in this thesis is the ability of sapB to bind a broader variety of ligands than has been previously shown. SapB is also shown to bind the bisretinoid A2E and prevent its enzymatic and photooxidation, with implications for the pathogenesis of Age-Related Macular Degeneration. Herein, it is also demonstrated that human patients taking the anti-malarial chloroquine have [sapB-chloroquine]complex in their urine, and the implications this has on the continued use of chloroquine treatment are discussed.

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