%0 Journal Article
%A Drebes, Julia
%A Künz, Madeleine
%A Windshügel, Björn
%A Kikhney, Alexey G.
%A Müller, Ingrid B.
%A Eberle, Raphael J.
%A Oberthür, Dominik
%A Cang, Huaixing
%A Svergun, Dmitri I.
%A Perbandt, Markus
%A Betzel, Christian
%A Wrenger, Carsten
%T Structure of ThiM from Vitamin B1 biosynthetic pathway of Staphylococcus aureus – Insights into a novel pro-drug approach addressing MRSA infections
%J Scientific reports
%V 6
%@ 2045-2322
%C London
%I Nature Publishing Group
%M PUBDB-2016-05650
%P 22871
%D 2016
%X 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.
%F PUB:(DE-HGF)16
%9 Journal Article
%U <Go to ISI:>//WOS:000371730400001
%$ pmid:26960569
%R 10.1038/srep22871
%U https://bib-pubdb1.desy.de/record/315123