| Full text | |
| Author(s): Show less - |
Drebes, Julia
[1, 2]
;
Kuenz, Madeleine
[1]
;
Windshuegel, Bjoern
[3]
;
Kikhney, Alexey G.
[4]
;
Mueller, Ingrid B.
[2]
;
Eberle, Raphael J.
[1, 5]
;
Oberthuer, Dominik
[1, 6]
;
Cang, Huaixing
[7]
;
Svergun, Dmitri I.
[4]
;
Perbandt, Markus
[1, 8]
;
Betzel, Christian
[1, 8]
;
Wrenger, Carsten
[9]
Total Authors: 12
|
| Affiliation: | [1] Univ Hamburg, DESY, Lab Struct Biol Infect & Inflammat, Hamburg - Germany
[2] Bernhard Nocht Inst Trop Med, Dept Biochem, Bernhard Nocht Str 74, D-20359 Hamburg - Germany
[3] Fraunhofer Inst Mol Biol & Appl Ecol IME, Hamburg - Germany
[4] EMBL Hamburg, DESY, Hamburg - Germany
[5] Univ Estadual Paulista, Multiuser Ctr Biomol Innovat, Dept Phys, UNESP, BR-15054000 Sao Jose Ddo Rio Preto, SP - Brazil
[6] DESY, Ctr Free Electron Laser Sci, Notkestr 85, D-22607 Hamburg - Germany
[7] Northwestern Polytech Univ, Sch Life Sci, Xian 710072, Shaanxi - Peoples R China
[8] Hamburg Ctr Ultrafast Imaging, Luruper Chaussee 149, D-22761 Hamburg - Germany
[9] Univ Sao Paulo, Dept Parasitol, Inst Biomed Sci, Unit Drug Discovery, Sao Paulo - Brazil
Total Affiliations: 9
|
| Document type: | Journal article |
| Source: | SCIENTIFIC REPORTS; v. 6, MAR 10 2016. |
| Web of Science Citations: | 3 |
| 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 (S alpha ThiM; EC 2.7.1.50), a potential target for pro-drug compounds and analyzed the native structure of S alpha ThiM and complexes with the natural substrate 5-(hydroxyethyl)-4-methylthiazole (THZ) and two selected substrate analogues. (AU) | |
| FAPESP's process: | 13/10288-1 - Analysis of the organelle biogenesis in Plasmodium falciparum by live cell imaging |
| Grantee: | Carsten Wrenger |
| Support type: | Regular Research Grants |