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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Structure of ThiM from Vitamin B1 biosynthetic pathway of Staphylococcus aureus - Insights into a novel pro-drug approach addressing MRSA infections

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Author(s):
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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