5coj
Structure of Hydroxyethylthiazole kinase ThiM from Staphylococcus aureus in complex with native substrate 2-(4-methyl-1,3-thiazol-5-yl)ethanol.Structure of Hydroxyethylthiazole kinase ThiM from Staphylococcus aureus in complex with native substrate 2-(4-methyl-1,3-thiazol-5-yl)ethanol.
Structural highlights
FunctionTHIM_STAAR Catalyzes the phosphorylation of the hydroxyl group of 4-methyl-5-beta-hydroxyethylthiazole (THZ). Publication Abstract from PubMedInfections 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. Structure 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 AG, Muller IB, Eberle RJ, Oberthur D, Cang H, Svergun DI, Perbandt M, Betzel C, Wrenger C Sci Rep. 2016 Mar 10;6:22871. doi: 10.1038/srep22871. PMID:26960569[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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