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000884297 1001_ $$0P:(DE-HGF)0$$aFurtmann, Fabia$$b0
000884297 245__ $$aCharacterization of the nucleotide-binding domain NsrF from the BceAB-type ABC-transporter NsrFP from the human pathogen Streptococcus agalactiae
000884297 260__ $$a[London]$$bMacmillan Publishers Limited, part of Springer Nature$$c2020
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000884297 520__ $$aTreatment of bacterial infections is a great challenge of our era due to the various resistance mechanisms against antibiotics. Antimicrobial peptides are considered to be potential novel compound as antibiotic treatment. However, some bacteria, especially many human pathogens, are inherently resistant to these compounds, due to the expression of BceAB-type ABC transporters. This rather new transporter family is not very well studied. Here, we report the first full characterization of the nucleotide binding domain of a BceAB type transporter from Streptococcus agalactiae, namely SaNsrF of the transporter SaNsrFP, which confers resistance against nisin and gallidermin. We determined the NTP hydrolysis kinetics and used molecular modeling and simulations in combination with small angle X-ray scattering to obtain structural models of the SaNsrF monomer and dimer. The fact that the SaNsrFH202A variant displayed no ATPase activity was rationalized in terms of changes of the structural dynamics of the dimeric interface. Kinetic data show a clear preference for ATP as a substrate, and the prediction of binding modes allowed us to explain this selectivity over other NTPs.
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000884297 7001_ $$00000-0002-6005-4372$$aPorta, Nicola$$b1
000884297 7001_ $$0P:(DE-HGF)0$$aHoang, Dai Tri$$b2
000884297 7001_ $$0P:(DE-HGF)0$$aReiners, Jens$$b3
000884297 7001_ $$0P:(DE-HGF)0$$aSchumacher, Julia$$b4
000884297 7001_ $$0P:(DE-HGF)0$$aGottstein, Julia$$b5
000884297 7001_ $$0P:(DE-Juel1)172663$$aGohlke, Holger$$b6
000884297 7001_ $$00000-0003-0780-9251$$aSmits, Sander H. J.$$b7$$eCorresponding author
000884297 773__ $$0PERI:(DE-600)2615211-3$$a10.1038/s41598-020-72237-7$$gVol. 10, no. 1, p. 15208$$n1$$p15208$$tScientific reports$$v10$$x2045-2322$$y2020
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