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Influence of NSAID Flurbiprofen on Protein Helix‐helix Interactions
Author(s) -
Gugala Natalie,
Turner Raymond J.
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.1092.3
Subject(s) - flurbiprofen , transmembrane protein , chemistry , membrane protein , integral membrane protein , helix (gastropod) , transmembrane domain , biophysics , protein–protein interaction , biochemistry , protein structure , alpha helix , leucine zipper , membrane , biology , peptide sequence , pharmacology , receptor , ecology , snail , gene
The mechanism of action of non‐steroidal anti‐inflammatory drugs (NSAIDs) is not fully understood, however, there is now some reports signifying that they may inter chelate into the membrane consequently influencing integral membrane protein folding. Given the recent appreciation of the microbiome, we considered investigating the influence of NSAIDS on the folding of bacterial multidrug resistance proteins. In this work, the Bacterial Adenylate Cyclase Two‐hybrid System (BACTH) was used to study the protein‐protein interactions of EmrE, from Escherichia coli , which is an inner integral membrane protein belonging to the Small Multi‐drug Resistant family. The in vivo BACTH assay was used as a technique to develop an enhanced understanding of the helix interactions of this protein as it resides within the membrane. In particular, a glycine motif found on helix 4 has been observed to be critical for the oligomerization and functionality of EmrE, in agreement to the known importance of these motifs in membrane proteins. In recent years it has been revealed that certain NSAIDs have the ability to bind to glycine motifs and enhance or disturb transmembrane segment interactions. Flurbiporfen, a common NSAID, was used in this work to explore if this drug would affect EmrE. Upon increasing concentrations of flurbiprofen it was found that the interactions between certain integral helix pairs were strengthened, whereas the interaction between the leucine zipper peptides, which was used as a positive for this work, demonstrated a decrease in helix interaction. Our work suggests that these drugs could influence bacterial protein structure and function.