Novel redox switch in proteins as therapeutic target
Targeting essential proteins in pathogens is an appealing way to combat infectious diseases. Scientists at the University of Göttingen discovered a novel and until now overlooked on/off switch that seems to be a ubiquitous regulatory element in proteins in all domains of life. They discovered a new class of Lysine–Cysteine redox switch with an NOS bridge, which regulates enzyme function. Ongoing work will focus on small molecules to selectively target and manipulate this novel switch as potential therapeutics.
To combat infectious diseases from pathogens like bacteria antibiotics are typically used, but this approach is threatened by evolution of antibiotic resistant pathogens. To identify new treatment options, scientists need to study the structure and mechanism of proteins that are key players in metabolism of the targeted pathogens.
Scientists at the University of Göttingen, Germany investigated a protein from the human pathogen Neisseria gonorrhoeae (Ng) that causes gonorrhea, a bacterial infection with over 100 million cases worldwide. The scientists studied the structure and mechanism of a key protein in the carbon metabolism (transaldolase). By doing so they identified a novel and unique N–O–S bridge. Like the S–S bridge, the N–O–S bridge can stabilize higher-order protein structures, and the formation of the N–O–S bridge is also chemically reversible (by oxidation and reduction = “redox switch”). Accordingly, the N–O–S bridge suggests new regulatory possibilities for proteins. An analysis of the protein structure database further disclosed many other proteins that very likely possess this switch. The new discovery of an adjustable redox switch might lead to the development of small molecules as potential drug candidates.
- new regulable target for pathogen treatment (new drug design)
- in silico drug design to enable specificity and sensitivity of new drugs
- development of new drugs to combat antibiotic resistance
New treatment option for viral or bacterial infectious diseases (e. g. COVID-19 or Gonorrhea).
In vitro feasibility studies of the first test substances were successfully completed.
A European patent application has been filed (applicant: Georg August University of Göttingen public law foundation).
- Marie Wensien et al.: A lysine–cysteine redox switch with an NOS bridge regulates enzyme function. Nature 2021. DoI: 10.1038/s41586-021-03513-3
- Fabian Rabe von Pappenheim et al.: NOS and SONOS redox switches in proteins. Nature Chemical Biology 2021 (preprint). DoI:10.21203/rs.3.rs-635771/v1)
Dr. Stefan Uhle
Patent Manager Life Sciences
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