Horizontally acquired HosA transcription factor bound with 4-hydroxy-benzoic acid exhibits unique tug-of-water dynamics

Abstract

AbstractPathogenicEscherichia coli(E. coli) causes serious illnesses in humans aided by several multiple antibiotic resistance regulator (MarR) transcription factors. Among these proteins, HosA provides support to these organisms by executing crucial roles in functions ranging from flagella motility to organic compound metabolism. The crystal structure of HosA from enteropathogenicE. coliis elucidated in this study along with conformational changes orchestrated by different amino acids due to para-hydroxy benzoic acid (PHB) binding in the hinge region. Structural analysis and extensive molecular dynamics simulation reveal role of a dynamic water molecule as a bridging entity in PHB bound structure which is not shown for any MarR structure yet. Also, it is shown that the HosA gene is transferred horizontally fromShigellato pathogenicE. coli, having 97.6% sequence similarity with an uncharacterized transcription factor fromShigella dysenteriae Sd197. This study may be promising to address several unanswered questions for the functioning of MarR transcription factors from infectiousE. coliand design inhibitors to combat these pathogens.