Effects of Desialylation on Human alpha1-Acid Glycoprotein-Ligand Interactions

Published

September 16, 2013

Author(s)

Richard Y. Huang, Jeffrey W. Hudgens

Abstract

Human α1-Acid Glycoprotein (AGP), an acute phase glycoprotein, exists predominantly in blood. With its ability to bind basic, lipophilic, and acidic drugs, AGP has served as a drug carrier. It has been shown that the carbohydrate composition of AGP changes in response to tissue injury, inflammation or infection, and can have great impact on AGP's drug-binding activities. The molecular-level details of the effects of desialylation on the AGP conformation and AGP-ligand interactions, however, are unknown. Here we report the use of hydrogen/deuterium exchange coupled with mass spectrometry (HDX-MS) to reveal the changes in AGP conformational dynamics induced by the removal of terminal sialic acid. HDX-MS also reveals the changes in conformational dynamics of sialylated and unsialylated AGP upon formation of holo-AGP-complexes with progesterone or propranolol. Our HDX-MS results demonstrate that desialylation stabilizes two loop regions that are exterior to the β-sheet barrel in AGP, and this stabilization minimizes the conformational changes of AGP upon binding with progesterone or propranolol.

Citation

Biochemistry

Volume

52

Issue

40

Pub Type

Journals

Download Paper

https://doi.org/10.1021/bi4011094

Local Download

Keywords

AGP, glycoprotein, human alpha1-acid, hydrogen/deuterium exchange, mass spectrometry, sialylation, progesterone, propranolol, HDX-ETD

Citation

Huang, R. and Hudgens, J. (2013), Effects of Desialylation on Human alpha1-Acid Glycoprotein-Ligand Interactions, Biochemistry, [online], https://doi.org/10.1021/bi4011094, https://tsapps.nist.gov/publication/get_pdf.cfm?pub_id=914495 (Accessed October 13, 2025)