Structure and mechanism of the cytochrome bd oxidase
The emergence of extensive and multidrug resistant pathogenic bacteria is becoming an ever-growing threat for global healthcare, posing serious clinical and societal challenges. A major survival factor in commensal and pathogenic bacteria is the cytochrome bd oxidase. This membrane-embedded enzyme is solely present in prokaryotes and found in almost all bacterial phylae. It acts as a terminal oxidase that catalyses the reduction of molecular oxygen to water in respiratory chains. Splitting of the dioxygen bond without formation of reactive oxygen species (ROS) and subsequent water formation by bd-type oxidases requires four electrons that are extracted from two substrate quinols per catalytic cycle. This exergonic reaction is coupled to the generation of an electrochemical proton gradient across the periplasmic membrane via vectorial release and uptake of protons. Cytochrome bd oxidases are structurally unrelated to heme-copper oxidases (HCO) including the well-known cytochrome c oxidases and distinguish themselves by a very high oxygen affinity and insensitivity to a variety of inhibitors as well as agents released by the human immune system. Hence, bd oxidases enable aerobic bacteria to colonise hostile environmental niches. Survival of pathogenic bacteria during infection, proliferation and the transition from acute to chronic states is intrinsically linked to bd oxidase abundance. Consequently, the bd oxidase is a highly attractive target for the development of a new generation of antimicrobial drugs.
|Date||Monday, 17 February 2020|
|Time||12:00pm - 1:00pm|
|Event Category||Health Sciences|
|Department||Biochemistry, Microbiology and Immunology|
|Location||Room 208, 2nd Floor Microbiology Building|
720 Cumberland St, Dunedin