Journal Article

PUBDB-2016-05650

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Structure of ThiM from Vitamin B1 biosynthetic pathway of Staphylococcus aureus – Insights into a novel pro-drug approach addressing MRSA infections

Drebes, J. (First author)EMBL* ; Künz, M.Extern* ; Windshügel, B. ; Kikhney, A. G. ; Müller, I. B. ; Eberle, R. J. ; Oberthür, D.CFEL*DESY* ; Cang, H. ; Svergun, D. I. ; Perbandt, M.EMBL* ; Betzel, C. (Corresponding author)Extern* ; Wrenger, C. (Corresponding author)

2016
Nature Publishing Group London

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Please use a persistent id in citations: doi:10.1038/srep22871  doi:10.3204/PUBDB-2016-05650

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.

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Contributing Institute(s):

1. Inst. f. Phys. Chemie (X-RAY)
2. EMBL-User (EMBL-User)
3. FS-CFEL-1 (Group Leader: Henry Chapman) (CFEL-I)

Research Program(s):

1. 6215 - Soft Matter, Health and Life Sciences (POF3-621) (POF3-621)
2. 6G3 - PETRA III (POF3-622) (POF3-622)
3. CUI - Hamburger Zentrum für ultraschnelle Beobachtung (194651731) (194651731)

Experiment(s):

1. PETRA Beamline P12 (PETRA III)
2. PETRA Beamline P14 (PETRA III)

Appears in the scientific report 2016

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Database coverage:
; ; ; ; BIOSIS Previews ; Current Contents - Physical, Chemical and Earth Sciences ; DOAJ Seal ; IF >= 5 ; JCR ; NCBI Molecular Biology Database ; SCOPUS ; Science Citation Index ; Science Citation Index Expanded ; Thomson Reuters Master Journal List ; Web of Science Core Collection ; Zoological Record

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