Download MendeleyStructure of ThiM from Vitamin B1 biosynthetic pathway of Staphylococcus aureus - Insights into a novel pro-drug approach addressing MRSA infections.
Drebes, J., Kunz, M., Windshugel, B., Kikhney, A.G., Muller, I.B., Eberle, R.J., Oberthur, D., Cang, H., Svergun, D.I., Perbandt, M., Betzel, C., Wrenger, C.(2016) Sci Rep 6: 22871-22871
- PubMed: 26960569
- DOI: https://doi.org/10.1038/srep22871
- Primary Citation of Related Structures:
5CGA, 5CGE, 5CM5, 5COJ - PubMed Abstract:
Infections caused by the methicillin-resistant Staphylococcus aureus (MRSA) are today known to be a substantial threat for global health. Emerging multi-drug resistant bacteria have created a substantial need to identify and discover new drug targets and to develop novel strategies to treat bacterial infections. A promising and so far untapped antibiotic target is the biosynthesis of vitamin B1 (thiamin). Thiamin in its activated form, thiamin pyrophosphate, is an essential co-factor for all organisms. Therefore, thiamin analogous compounds, when introduced into the vitamin B1 biosynthetic pathway and further converted into non-functional co-factors by the bacterium can function as pro-drugs which thus block various co-factor dependent pathways. We characterized one of the key enzymes within the S. aureus vitamin B1 biosynthetic pathway, 5-(hydroxyethyl)-4-methylthiazole kinase (SaThiM; EC 2.7.1.50), a potential target for pro-drug compounds and analyzed the native structure of SaThiM and complexes with the natural substrate 5-(hydroxyethyl)-4-methylthiazole (THZ) and two selected substrate analogues.
Organizational Affiliation:
University Hamburg, c/o DESY, Laboratory for Structural Biology of Infection and Inflammation, Hamburg, Germany.
