Publikation: Crystal structure of the antibiotic albomycin in complex with the outer membrane transporter FhuA
Dateien
Datum
Autor:innen
Herausgeber:innen
ISSN der Zeitschrift
Electronic ISSN
ISBN
Bibliografische Daten
Verlag
Schriftenreihe
Auflagebezeichnung
URI (zitierfähiger Link)
DOI (zitierfähiger Link)
Internationale Patentnummer
Link zur Lizenz
Angaben zur Forschungsförderung
Projekt
Open Access-Veröffentlichung
Sammlungen
Core Facility der Universität Konstanz
Titel in einer weiteren Sprache
Publikationstyp
Publikationsstatus
Erschienen in
Zusammenfassung
One alternative method for drug delivery involves the use of siderophore-antibiotic conjugates. These compounds represent a specific means by which potent antimicrobial agents, covalently linked to iron-chelating siderophores, can be actively transported across the outer membrane of Gram-negative bacteria. These Trojan Horse antibiotics may prove useful as an efficient means to combat multi-drug resistant bacterial infections. Here we present the crystallographic structures of the natural siderophore-antibiotic conjugate albomycin and the siderophore phenylferricrocin, in complex with the active outer membrane transporter FhuA from Escherichia coli. To our knowledge, this represents the first structure of an antibiotic bound to its cognate transporter. Albomycins are broad-host range antibiotics that consist of a hydroxamate-type iron-chelating siderophore, and an antibiotically active, thioribosyl pyrimidine moiety. As observed with other hydroxamate-type siderophores, the three-dimensional structure of albomycin reveals an identical coordination geometry surrounding the ferric iron atom. Unexpectedly, this antibiotic assumes two conformational isomers in the binding site of FhuA, an extended and a compact form. The structural information derived from this study provides novel insights into the diverse array of antibiotic moieties that can be linked to the distal portion of iron-chelating siderophores and offers a structural platform for the rational design of hydroxamate-type siderophore-antibiotic conjugates.
Zusammenfassung in einer weiteren Sprache
Fachgebiet (DDC)
Schlagwörter
Konferenz
Rezension
Zitieren
ISO 690
FERGUSON, Andrew M., Volkmar BRAUN, Hans-Peter FIEDLER, James W. COULTON, Kay DIEDERICHS, Wolfram WELTE, 2000. Crystal structure of the antibiotic albomycin in complex with the outer membrane transporter FhuA. In: Protein Science. 2000, 9(5), pp. 956-963. ISSN 0961-8368. eISSN 1469-896X. Available under: doi: 10.1110/ps.9.5.956BibTex
@article{Ferguson2000Cryst-7495, year={2000}, doi={10.1110/ps.9.5.956}, title={Crystal structure of the antibiotic albomycin in complex with the outer membrane transporter FhuA}, number={5}, volume={9}, issn={0961-8368}, journal={Protein Science}, pages={956--963}, author={Ferguson, Andrew M. and Braun, Volkmar and Fiedler, Hans-Peter and Coulton, James W. and Diederichs, Kay and Welte, Wolfram} }
RDF
<rdf:RDF xmlns:dcterms="http://purl.org/dc/terms/" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:bibo="http://purl.org/ontology/bibo/" xmlns:dspace="http://digital-repositories.org/ontologies/dspace/0.1.0#" xmlns:foaf="http://xmlns.com/foaf/0.1/" xmlns:void="http://rdfs.org/ns/void#" xmlns:xsd="http://www.w3.org/2001/XMLSchema#" > <rdf:Description rdf:about="https://kops.uni-konstanz.de/server/rdf/resource/123456789/7495"> <foaf:homepage rdf:resource="http://localhost:8080/"/> <dcterms:available rdf:datatype="http://www.w3.org/2001/XMLSchema#dateTime">2011-03-24T17:34:53Z</dcterms:available> <dcterms:hasPart rdf:resource="https://kops.uni-konstanz.de/bitstream/123456789/7495/1/41_albo_protsci.pdf"/> <dc:contributor>Ferguson, Andrew M.</dc:contributor> <dc:contributor>Braun, Volkmar</dc:contributor> <dcterms:rights rdf:resource="http://creativecommons.org/licenses/by-nc-nd/2.0/"/> <dcterms:isPartOf rdf:resource="https://kops.uni-konstanz.de/server/rdf/resource/123456789/28"/> <dcterms:bibliographicCitation>First publ. in: Protein Science 9 (2000), pp. 956-963</dcterms:bibliographicCitation> <dc:contributor>Fiedler, Hans-Peter</dc:contributor> <dc:creator>Coulton, James W.</dc:creator> <dc:contributor>Coulton, James W.</dc:contributor> <dcterms:abstract xml:lang="eng">One alternative method for drug delivery involves the use of siderophore-antibiotic conjugates. These compounds represent a specific means by which potent antimicrobial agents, covalently linked to iron-chelating siderophores, can be actively transported across the outer membrane of Gram-negative bacteria. These Trojan Horse antibiotics may prove useful as an efficient means to combat multi-drug resistant bacterial infections. Here we present the crystallographic structures of the natural siderophore-antibiotic conjugate albomycin and the siderophore phenylferricrocin, in complex with the active outer membrane transporter FhuA from Escherichia coli. To our knowledge, this represents the first structure of an antibiotic bound to its cognate transporter. Albomycins are broad-host range antibiotics that consist of a hydroxamate-type iron-chelating siderophore, and an antibiotically active, thioribosyl pyrimidine moiety. As observed with other hydroxamate-type siderophores, the three-dimensional structure of albomycin reveals an identical coordination geometry surrounding the ferric iron atom. Unexpectedly, this antibiotic assumes two conformational isomers in the binding site of FhuA, an extended and a compact form. The structural information derived from this study provides novel insights into the diverse array of antibiotic moieties that can be linked to the distal portion of iron-chelating siderophores and offers a structural platform for the rational design of hydroxamate-type siderophore-antibiotic conjugates.</dcterms:abstract> <dc:creator>Ferguson, Andrew M.</dc:creator> <dc:contributor>Welte, Wolfram</dc:contributor> <dcterms:title>Crystal structure of the antibiotic albomycin in complex with the outer membrane transporter FhuA</dcterms:title> <dspace:isPartOfCollection rdf:resource="https://kops.uni-konstanz.de/server/rdf/resource/123456789/28"/> <dc:creator>Diederichs, Kay</dc:creator> <dspace:hasBitstream rdf:resource="https://kops.uni-konstanz.de/bitstream/123456789/7495/1/41_albo_protsci.pdf"/> <dc:creator>Welte, Wolfram</dc:creator> <dc:language>eng</dc:language> <dc:contributor>Diederichs, Kay</dc:contributor> <dc:rights>Attribution-NonCommercial-NoDerivs 2.0 Generic</dc:rights> <void:sparqlEndpoint rdf:resource="http://localhost/fuseki/dspace/sparql"/> <dc:date rdf:datatype="http://www.w3.org/2001/XMLSchema#dateTime">2011-03-24T17:34:53Z</dc:date> <dc:creator>Braun, Volkmar</dc:creator> <bibo:uri rdf:resource="http://kops.uni-konstanz.de/handle/123456789/7495"/> <dc:creator>Fiedler, Hans-Peter</dc:creator> <dc:format>application/pdf</dc:format> <dcterms:issued>2000</dcterms:issued> </rdf:Description> </rdf:RDF>