Lecture
L(SB)2 Seminar: Menaquinone-specific oxidation by M. tuberculosis cytochrome bd is redox regulated by the Q-loop disulfide bond
- Date
- Thursday 31 October 2024
- Time
- Location
-
Gorlaeus Building
Einsteinweg 55
2333 CC Leiden - Room
- BE.0.10
We would like to invite you to a new seminar series that aims to bring together all researchers in Leiden that are interested in biophysics and structural biology. L(SB)2, the Leiden Seminars in Biophysics and Structural Biology, takes place monthly and combines presentations of talented PhD students from Leiden University with talks of PIs from other Dutch or international universities. We hope to see many of you there!
Abstract
Cytochrome bd from Mycobacterium tuberculosis (Mtbd) is a menaquinol oxidase that has gained interest as an antibiotic target due to its importance in survival under infectious conditions. Mtbd contains a characteristic disulfide bond that has been hypothesized to allow for Mtbd activity regulation at the enzymatic level, allowing M. tuberculosis to rapidly adapt to hostile conditions. Here, the role of the disulfide bond and quinone specificity have been determined by reconstitution of a minimal respiratory chain and the single-particle cryo-EM structure in the disulphide reduced form. Mtbd was shown to be specific for menaquinone, while regulation by reduction of the Q-loop disulfide bond decreased oxidase activity up to 90%. Structural analysis shows that a salt bridge unique to Mtbd keeps the Q-loop partially structured in its disulphide-reduced form, which could facilitate the rapid activation of Mtbd upon exposure reactive oxygen species. We signify Mtbd as the first redox sensory terminal oxidase and propose that this helps M. tuberculosis in the defence against reactive oxygen species encountered during infection.