The Asp99-Arg188 salt bridge of the Pseudomonas aeruginosa HemO is critical in allowing conformational flexibility during catalysis.

ABSTRACT: The P. aeruginosa iron-regulated heme oxygenase (HemO) is required within the host for the utilization of heme as an iron source. As iron is essential for survival and virulence, HemO represents a novel antimicrobial target. We recently characterized small molecule inhibitors that bind to an allosteric site distant from the heme pocket, and further proposed binding at this site disrupts a nearby salt bridge between D99 and R188. Herein, through a combination of site-directed mutagenesis and hydrogen-deuterium exchange mass spectrometry (HDX-MS), we determined that the disruption of the D99-R188 salt bridge leads to significant decrease in conformational flexibility within the distal and proximal helices that form the heme-binding site. The RR spectra of the resting state Fe(III) and reduce

SUBMITTER: Heinzl GA 

PROVIDER: S-EPMC6203605 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature