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doi:10.22028/D291-39227
Titel: | Protein-observed 19F NMR of LecA from Pseudomonas aeruginosa |
VerfasserIn: | Shanina, Elena Siebs, Eike Zhang, Hengxi Varón Silva, Daniel Joachim, Ines Titz, Alexander Rademacher, Christoph |
Sprache: | Englisch |
Titel: | Glycobiology |
Bandnummer: | 31 (2021) |
Heft: | 2 |
Seiten: | 159-165 |
Verlag/Plattform: | Oxford University Press |
Erscheinungsjahr: | 2020 |
Freie Schlagwörter: | drug discovery LecA lectin NMR |
DDC-Sachgruppe: | 500 Naturwissenschaften |
Dokumenttyp: | Journalartikel / Zeitschriftenartikel |
Abstract: | The carbohydrate-binding protein LecA (PA-IL) from Pseudomonas aeruginosa plays an important role in the formation of biofilms in chronic infections. Development of inhibitors to disrupt LecAmediated biofilms is desired but it is limited to carbohydrate-based ligands. Moreover, discovery of drug-like ligands for LecA is challenging because of its weak affinities. Therefore, we established a protein-observed 19F (PrOF) nuclear magnetic resonance (NMR) to probe ligand binding to LecA. LecA was labeled with 5-fluoroindole to incorporate 5-fluorotryptophanes and the resonances were assigned by site-directed mutagenesis. This incorporation did not disrupt LecA preference for natural ligands, Ca2+ and D-galactose (D-Gal). Following NMR perturbation of W42, which is located in the carbohydrate-binding region of LecA, allowed to monitor binding of low-affinity ligands such as N-acetyl D-galactosamine (D-GalNAc, Kd = 780 ± 97 μM). Moreover, PrOF NMR titration with glycomimetic of LecA p-nitrophenyl β-D-galactoside (pNPGal, Kd = 54 ± 6 μM) demonstrated a 6-fold improved binding of D-Gal proving this approach to be valuable for ligand design in future drug discovery campaigns that aim to generate inhibitors of LecA. |
DOI der Erstveröffentlichung: | 10.1093/glycob/cwaa057 |
URL der Erstveröffentlichung: | https://doi.org/10.1093/glycob/cwaa057 |
Link zu diesem Datensatz: | urn:nbn:de:bsz:291--ds-392278 hdl:20.500.11880/35351 http://dx.doi.org/10.22028/D291-39227 |
ISSN: | 1460-2423 |
Datum des Eintrags: | 6-Mär-2023 |
Bezeichnung des in Beziehung stehenden Objekts: | Supplementary data |
In Beziehung stehendes Objekt: | https://oup.silverchair-cdn.com/oup/backfile/Content_public/Journal/glycob/31/2/10.1093_glycob_cwaa057/1/supplementary_information_revised_cwaa057.pdf?Expires=1681118617&Signature=1xmBNFr4heBsnxB~KjWberDyo8a8VGFhWyBw5dfRG~1f37LcUdP4QlhqweTbfpyTKFq017nUDOoRbu8HPnMleyePAGVJpq-GfQy9mSs3aQYb8ocXvOeRaE0P8YGqzsSX0Onao3FD8BqPQCELWzTFyScLGarXXr9qvcNikBEWusalM6eEwyKOMGiW2VqXAICptHSb9IwU1yIVI39pkry~fI8ReRA7bLdm4lCSDkgXNwDgqvKmCvbnj~PKE4toDgXRad7pKH~6QUEuHl1l6BlfxBZZGkTcv326elK~GPWS4PG9X6UDtpOK1~BmUShDS2EZouzZKXWWCbHNAdcc8UfqGg__&Key-Pair-Id=APKAIE5G5CRDK6RD3PGA https://oup.silverchair-cdn.com/oup/backfile/Content_public/Journal/glycob/31/2/10.1093_glycob_cwaa057/1/glyco-2020-00049_revision_cwaa057.docx?Expires=1681118617&Signature=alnjXm5u-BfhLF9b-A3ERezckSEoSUk~cEaKgSVnyPz3-PK9jKMGbi2TMmcobvvenPuq3ubo36C-0YL5oQYPgQaUyabRz-04JbFISaan5qPUDzkx1pAgJJiadKQgxE29tVhcICbhmc3Sl47Erf1l3pn18RfsVBzSTJpb~CQG2jG3w52S9bb5avi9NEJ61V1K5H9cfthisz6Z79EALual2t1rds9b44tCHeow3QYmIRuq14YAA4iSnqL7il~t22QFEOzorI0dVsaQknpJqo-iAUIlgUvCEueJeHuIsfmFAUAsKktHiLnqvmGUFUofllBpd47~6UpPlVVO6BHQJylP3w__&Key-Pair-Id=APKAIE5G5CRDK6RD3PGA |
Fakultät: | NT - Naturwissenschaftlich- Technische Fakultät |
Fachrichtung: | NT - Chemie |
Professur: | NT - Univ.-Prof. Dr. phil. Alexander Titz |
Sammlung: | SciDok - Der Wissenschaftsserver der Universität des Saarlandes |
Dateien zu diesem Datensatz:
Datei | Beschreibung | Größe | Format | |
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cwaa057.pdf | 3,71 MB | Adobe PDF | Öffnen/Anzeigen |
Diese Ressource wurde unter folgender Copyright-Bestimmung veröffentlicht: Lizenz von Creative Commons