Mutational Analysis of Quinolone Resistance Protein QnrVC7 Provides Novel Insights into the Structure-Activity Relationship of Qnr Proteins

Abstract

This study assessed the functional importance of residues located at the i(-2) position of face 4 of the tandem repeat loops of the quinolone resistance protein QnrVC7 through mutagenesis studies. The i(-2) position of face 4 on different coils required residues with different natures. Some substitutions reduced the protective activity of QnrVC7, while some of them increased it. These findings advanced our understanding on the detailed structural organization and functional requirements of Qnr proteins.

FIG 1

Amino acid sequence and structural representation of QnrVC7 and specific mutant proteins. (A) Tabular array of QnrV7 amino acids grouped by pentapeptide repeats, with coils along the vertical axis and faces along the horizontal axis; i⁻² residues characterized in this study are in bold. (B) Overall structure of QnrVC7 and its organization. The sites at the i⁻² position of face 4 are indicated in purple. (C) Amino acid substitutions that led to an increase in protective activity of QnrVC7. The potential hydrophobic interactions that may enhance the stability of QnrVC7 are indicated in gray and purple.