5CGA
Structure of Hydroxyethylthiazole kinase ThiM from Staphylococcus aureus in complex with substrate analog 2-(1,3,5-trimethyl-1H-pyrazole-4-yl)ethanol
Summary for 5CGA
| Entry DOI | 10.2210/pdb5cga/pdb |
| Descriptor | Hydroxyethylthiazole kinase, 2-(1,3,5-trimethyl-1H-pyrazol-4-yl)ethanol, MAGNESIUM ION, ... (4 entities in total) |
| Functional Keywords | bacterial thiamine biosynthesis, hydroxyethylthiazole kinase, substrate analog, transferase |
| Biological source | Staphylococcus aureus MRSA252 |
| Total number of polymer chains | 6 |
| Total formula weight | 179875.03 |
| Authors | Kuenz, M.,Drebes, J.,Windshuegel, B.,Cang, H.,Wrenger, C.,Betzel, C. (deposition date: 2015-07-09, release date: 2016-03-23, Last modification date: 2024-05-08) |
| Primary citation | 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. Structure of ThiM from Vitamin B1 biosynthetic pathway of Staphylococcus aureus - Insights into a novel pro-drug approach addressing MRSA infections. Sci Rep, 6:22871-22871, 2016 Cited by 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. PubMed: 26960569DOI: 10.1038/srep22871 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.87 Å) |
Structure validation
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