Binding interactions between enantiomeric α-aminophosphonate derivatives and tobacco mosaic virus coat protein

• Published in: International journal of biological macromolecules Vol. 94; no. Pt A; pp. 603 - 610
• Main Authors: Zhang, Weiying, Li, Xiangyang, Zhang, Guoping, Ding, Yan, Ran, Longlu, Luo, Liangzhi, Wu, Jian, Hu, Deyu, Song, Baoan
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.01.2017
• Subjects: Amino Acid Substitution; Antiviral Agents - chemical synthesis; Antiviral Agents - chemistry; Arg90; Arginine - chemistry; Capsid Proteins - chemistry; Capsid Proteins - genetics; Enantiomeric α-aminophosphonate derivatives; Gene Expression; Glycine - chemistry; Interactions; Molecular Docking Simulation; Organophosphonates - chemical synthesis; Organophosphonates - chemistry; Protein Binding; Protein Structure, Secondary; Recombinant Proteins - chemistry; Recombinant Proteins - genetics; Spectrometry, Fluorescence; Stereoisomerism; Structure-Activity Relationship; TMV CP; Tobacco Mosaic Virus - chemistry; Interactions; TMV CP; Arg90; Enantiomeric α-aminophosphonate derivatives
• ISSN: 0141-8130; 1879-0003
• DOI: 10.1016/j.ijbiomac.2016.10.027

•The binding force of enantiomeric α-aminophosphonate derivatives with TMV CP is R isomer >S isomer.•Compound Q-Rinteracts with Arg90 of TMV CP through strong hydrogen bonding.•Substituting arginine with glycine affects the binding affinity of the Q-Rand TMV CP.•The reassembly TMV R90G virus particle resulted in a loss of its ability to infect tobacco. Tobacco mosaic virus (TMV) is an important plant virus that can cause considerable crop loss. Our group synthesized a series of enantiomeric α-aminophosphonate derivatives with high anti-TMV activities. The activity of (R)-diphenyl-1-(4-methylbenzothiazole-2-amino)-1-(thiphene-2-yl)-methylphosphonate (Q-R) was found to be superior to that of (S)-diphenyl-1-(4-methyl benzothiazole-2-amino)-1-(thiphene-2-yl)-methylphosphonate (Q-S). However, the mechanism for inhibition of the R-isomer (Q-R) of infection activity is not clear. Thus, we studied the interactions between Q-R and Q-S and TMV by using TMV coat proteins (CP) as a potential target for fluorescence spectroscopy, isothermal titration calorimetry, microscale thermophoresis, and molecular docking. Arg90 was found to play a major role in the interaction of Q-R with TMV CP, as demonstrated by the interaction experiments and the results of molecular modeling. The substitution of arginine with glycine resulted in a mutant that was significantly less sensitive to Q-R. These results indicate that Q-R undermines the structural stability of the TMV R90G virus particle by binding with Arg90, eventually leading to the loss of the virus’ ability for infection.