Effects of desialylation on human α1-acid glycoprotein-ligand interactions

Biochemistry. 2013 Oct 8;52(40):7127-36. doi: 10.1021/bi4011094. Epub 2013 Sep 27.


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 a 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 the conformational dynamics of sialylated and unsialylated AGP upon formation of complexes of holo-AGP 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Deuterium Exchange Measurement
  • Glycosylation
  • Humans
  • Ligands
  • Mass Spectrometry
  • N-Acetylneuraminic Acid / chemistry*
  • Orosomucoid / chemistry*
  • Orosomucoid / metabolism*
  • Progesterone / metabolism
  • Propranolol / metabolism
  • Protein Conformation


  • Ligands
  • Orosomucoid
  • Progesterone
  • Propranolol
  • N-Acetylneuraminic Acid