5CGE

Structure of Hydroxyethylthiazole Kinase ThiM from Staphylococcus aureus in complex with substrate analog 2-(2-methyl-1H-imidazole-1-yl)ethanol

Summary for 5CGE

• Entry DOI: 10.2210/pdb5cge/pdb
• Related: 5CGA
• Descriptor: Hydroxyethylthiazole kinase, 2-(2-methyl-1H-imidazol-1-yl)ethanol, MAGNESIUM ION, ... (4 entities in total)
• Functional Keywords: bacterial thiamine biosynthesis, hydroxyethylthiazole kinase, substrate analog, transferase
• Biological source: Staphylococcus aureus subsp. aureus MRSA252
• Total number of polymer chains: 6
• Total formula weight: 179845.27

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

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: 26960569
DOI: 10.1038/srep22871

Experimental method

X-RAY DIFFRACTION (1.62 Å)