dc.contributor.author
Rostock, Linda
dc.contributor.author
Driller, Ronja
dc.contributor.author
Grätz, Stefan
dc.contributor.author
Kerwat, Dennis
dc.contributor.author
Eckardstein, Leonard von
dc.contributor.author
Daniel, Petras
dc.contributor.author
Kunert, Maria
dc.contributor.author
Alings, Claudia
dc.contributor.author
Schmitt, Franz-Josef
dc.contributor.author
Friedrich, Thomas
dc.contributor.author
Wahl, Markus C.
dc.contributor.author
Loll, Bernhard
dc.contributor.author
Mainz, Andi
dc.contributor.author
Süssmuth, Roderich D.
dc.date.accessioned
2018-09-05T08:24:45Z
dc.date.available
2018-09-05T08:24:45Z
dc.identifier.uri
https://refubium.fu-berlin.de/handle/fub188/22807
dc.identifier.uri
http://dx.doi.org/10.17169/refubium-605
dc.description.abstract
The worldwide emergence of antibiotic resistance poses a serious threat to human health. A molecular understanding of resistance strategies employed by bacteria is obligatory to generate less-susceptible antibiotics. Albicidin is a highly potent antibacterial compound synthesized by the plant-pathogenic bacterium Xanthomonas albilineans. The drug-binding protein AlbA confers albicidin resistance to Klebsiella oxytoca. Here we show that AlbA binds albicidin with low nanomolar affinity resulting in full inhibition of its antibacterial activity. We report on the crystal structure of the drug-binding domain of AlbA (AlbAS) in complex with albicidin. Both α-helical repeat domains of AlbAS are required to cooperatively clamp albicidin, which is unusual for drug-binding proteins of the MerR family. Structure-guided NMR binding studies employing synthetic albicidin derivatives give valuable information about ligand promiscuity of AlbAS. Our findings thus expand the general understanding of antibiotic resistance mechanisms and support current drug-design efforts directed at more effective albicidin analogs.
en
dc.format.extent
13 Seiten
de_DE
dc.rights.uri
https://creativecommons.org/licenses/by/4.0/
de_DE
dc.subject
Biochemistry
en
dc.subject
Biophysical chemistry
en
dc.subject
DNA-binding proteins
en
dc.subject
Structural biology
en
dc.subject.ddc
500 Naturwissenschaften und Mathematik::570 Biowissenschaften; Biologie::572 Biochemie
de_DE
dc.title
Molecular insights into antibiotic resistance - how a binding protein traps albicidin
de_DE
dc.type
Wissenschaftlicher Artikel
de_DE
dcterms.bibliographicCitation.articlenumber
3095
dcterms.bibliographicCitation.journaltitle
Nature Communications
dcterms.bibliographicCitation.volume
9
dcterms.bibliographicCitation.url
https://doi.org/10.1038/s41467-018-05551-4
de_DE
refubium.affiliation
Biologie, Chemie, Pharmazie
de_DE
refubium.affiliation.other
Institut für Chemie und Biochemie
de_DE
refubium.note.author
Der Artikel wurde in einer reinen Open-Access-Zeitschrift publiziert.
de_DE
refubium.resourceType.isindependentpub
no
de_DE
dcterms.accessRights.openaire
open access
dcterms.isPartOf.issn
2041-1723