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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

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