All organisms from humans to bacteria that respire oxygen contain large respiratory complexes. These complexes require metal ions and other molecules called quinones to cycle electrons and hydrogen ions while extracting energy from nutrients and oxygen to drive all biological processes in the cells. Because of their essential role, these respiratory complexes are very attractive targets for developing new antibiotics.

In the study entitled Structure of a functional obligate complex III₂IV₂ respiratory supercomplex from Mycobacterium smegmatis, the researchers were able to visualize atomic details and record snapshots of the respiratory supercomplex in action. This remarkable new structure contains eleven enzymes that come together to form a large supercomplex and reveals many intriguing features unique to Mycobacteria that could be exploited to develop new antibiotics targeting this deadly pathogen.

One such feature is a quinone binding site that is unique to Mycobacteria. Targeting this binding site could create drugs that specifically inhibit the mycobacterial complex without affecting the human version. There are already tuberculosis drugs targeting this complex in clinical trials and this new structure can confirm their mode of action and potentially improve their effectiveness and reduce off-target effects.

Link to the study:

https://www.nature.com/articles/s41594-018-0160-3

For further information

Peter Brzezinski and Martin Högbom, professors at the Department of Biochemistry and Biophysics, Stockholm University

hogbom@dbb.su.se      phone: 070 4132806

peterb@dbb.su.se         phone:  070 609 2642

About the study

Structure of a functional obligate complex III₂IV₂ respiratory supercomplex from Mycobacterium smegmatis is a collaboration between researchers at Stockholm University and The Hospital for Sick Children in Toronto, Canada.