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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

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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Autor(es):
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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]
Número total de Autores: 12
Afiliação do(s) autor(es):
[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
Número total de Afiliações: 9
Tipo de documento: Artigo Científico
Fonte: SCIENTIFIC REPORTS; v. 6, MAR 10 2016.
Citações Web of Science: 3
Resumo

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)

Processo FAPESP: 13/10288-1 - Análise da biogênese de organelas em Plasmodium falciparum por visualização celular em tempo real
Beneficiário:Carsten Wrenger
Linha de fomento: Auxílio à Pesquisa - Regular