Interaction study of the antibacterial peptide urumin with the H1N1 HA protein of influenza A virus
10.16438/j.0513-4870.2021-0483
- VernacularTitle:抗菌肽urumin与甲型流感病毒H1N1 HA蛋白的相互作用研究
- Author:
Hong-mei LI
1
;
Wei-juan ZHENG
1
;
Jia-huang LI
2
;
Zi-chun HUA
2
Author Information
1. State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210023, China
2. State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210023, China; College of Biopharmaceuticals, China Pharmaceutical University, Nanjing 211198, China; High-tech Research Institute of Nanjing University at Changzhou and Jiangsu Target Pharma Laboratories Inc., Changzhou 213164, China
- Publication Type:Research Article
- Keywords:
urumin peptide;
H1N1 virus;
hemagglutinin;
molecular docking simulation;
binding site
- From:
Acta Pharmaceutica Sinica
2021;56(9):2553-2560
- CountryChina
- Language:Chinese
-
Abstract:
Influenza A virus (H1N1) seriously affects the health of human and disrupts the development of global economic. The antimicrobial peptide urumin specifically binds to the conserved stem of the hemagglutinin (HA) protein of H1N1 virus, but its binding site and the mechanism of action are not clear. In this study, we investigated the possible binding sites and key amino acids for the interaction of urumin with HA protein by molecular docking and enzyme-linked immunosorbent assay (ELISA) experiments, suggesting that HA residues His32 (HA1), Asp19 (HA2), and Trp21 (HA2) are the key residues for the interaction of HA with urumin. Urumin's Arg4, Asn9, and Cys16 were associated with HA protein residues Asp19 (HA2), Trp21 (HA2), His32 (HA1), and Asn53 (HA2) form hydrogen bonding interactions, and Trp12 forms an aromatic π-stacking interaction with His32 (HA1) of HA, these interactions maintain the binding of urumin to HA protein. Wild-type HA and its alanine mutant [alanine substitutions His32 (HA1), Asp19 (HA2), and Trp21 (HA2)] were expressed in 293T cells. ELISA experiments showed that the affinity ability of urumin with HA wild-type was significantly higher than that of HA alanine mutant, suggesting that His32 (HA1), Asp19 (HA2), and Trp21 (HA2) may be the key residues for HA to interact with urumin. This study provides a theoretical and experimental basis for further modification and application of urumin.
