An official website of the United States government
Here’s how you know
Official websites use .gov
A .gov website belongs to an official government organization in the United States.
Secure .gov websites use HTTPS
A lock (
) or https:// means you’ve safely connected to the .gov website. Share sensitive information only on official, secure websites.
Effects of Desialylation on Human alpha1-Acid Glycoprotein-Ligand Interactions
Published
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.
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 November 11, 2024)