The role of conserved arginine and proline residues in enterovirus VP1 protein.

BACKGROUND

High diversity of VP1 protein among enteroviruses has been a barrier in developing universally effective antiviral drugs. To maintain structure stability during evolution, several residues of VP1 protein of enteroviruses are conserved. Therefore, investigation of highly conserved residues in VP1 protein may provide information for antiviral drug candidates against enteroviruses.

METHODS

To identify highly conserved amino acid sequences of the VP1 in enterovirus genus, the Consurf and CABS-flex 2.0 web software were applied. Through the combination with secondary structure information, we focused on conserved amino acids of VP1 property analysis.

RESULTS

Most conserved residues of VP1 were in the interior and interacted with VP2, VP3 and VP4 capsid proteins. Structure of EV-A71 (PDB code 4AED) showed conserved residues were at hydrophobic pocket and close to the junction between the loop and β-barrel. Interestingly, arginine was the most common conserved residue of VP1. Proline was the second most common conserved residue and was found in the loop and β-barrel intersection areas. VP1 protein flexibility was associated with the secondary structure. Conserved residues of VP1 in β-barrel showed significantly low flexibility.

CONCLUSION

Through large scale sequence analysis, we identified the amino acid distribution and location of conserved residues in VP1. This knowledge can be extrapolated for the Enterovirus genus and may contribute to developing the potential compound as an anti-enteroviral agent.