7ER3

Crystal structure of beta-lactoglobulin complexed with chloroquine

Summary for 7ER3

• Entry DOI: 10.2210/pdb7er3/pdb
• Descriptor: Major allergen beta-lactoglobulin, (4S)-N~4~-(7-chloroquinolin-4-yl)-N~1~,N~1~-diethylpentane-1,4-diamine (3 entities in total)
• Functional Keywords: beta-lactoglobulin, chloroquine, immune system
• Biological source: Bos taurus (Bovine)
• Total number of polymer chains: 4
• Total formula weight: 74828.54

Authors

Yao, Q.,Ma, J.,Xing, Y.,Zang, J. (deposition date: 2021-05-05, release date: 2022-05-18, Last modification date: 2024-10-16)

Primary citation

Yao, Q.,Xing, Y.,Ma, J.,Wang, C.,Zang, J.,Zhao, G.
Binding of Chloroquine to Whey Protein Relieves Its Cytotoxicity while Enhancing Its Uptake by Cells.
J.Agric.Food Chem., 69:10669-10677, 2021

PubMed Abstract: Chloroquine (CQ) is a famous medicine for treatment of diseases including malaria and pneumonia caused by COVID-19, but gastrointestinal disorder caused by its oral administration is a great concern. Milk is usually recommended to be taken with CQ to reduce such effect. However, the mechanism underlying this phenomenon remains unknown. Here, we found that β-lactoglobulin (β-LG), α-lactalbumin (α-LA), bovine serum albumin (BSA), and lactoferrin (LF) in whey proteins were able to interact with CQ to form complexes as suggested by fluorescence resonance energy transfer (FRET) and molecular docking. Indeed, the crystal structure revealed that β-LG is bound to CQ through hydrophobic interactions and hydrogen bonding with a ratio of 1:1. Consequently, the formation of these protein-CQ complexes not only reduced the cytotoxicity of chloroquine to the stomach and gut cells but also facilitated its uptake by cells. This work gave an example to understand the relationship between food and drug.

PubMed: 34463093
DOI: 10.1021/acs.jafc.1c04140

Experimental method

X-RAY DIFFRACTION (2.598 Å)