Dokument: Structural insights into the substrate binding mechanism of the class I dehydratase MadB
| Titel: | Structural insights into the substrate binding mechanism of the class I dehydratase MadB | |||||||
| URL für Lesezeichen: | https://docserv.uni-duesseldorf.de/servlets/DocumentServlet?id=70244 | |||||||
| URN (NBN): | urn:nbn:de:hbz:061-20250718-100006-8 | |||||||
| Kollektion: | Publikationen | |||||||
| Sprache: | Englisch | |||||||
| Dokumententyp: | Wissenschaftliche Texte » Artikel, Aufsatz | |||||||
| Medientyp: | Text | |||||||
| Autoren: | Knospe, Christina Vivien [Autor] Ortiz, Julio [Autor] Reiners, Jens [Autor] Kedrov, Alexej [Autor] Gertzen, Christoph G.W. [Autor] Smits, Sander H.J. [Autor] Schmitt, Lutz [Autor] | |||||||
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| Beschreibung: | In the battle against antimicrobial resistance, lantibiotics have emerged as promising new sources for antimicrobial drugs. Their exceptional stability is due to characteristic modifications termed (methyl-)lanthionine rings. Genome mining efforts have identified hundreds of lantibiotics by detecting gene operons, so-called biosynthetic gene clusters (BGC), which encode cysteine-rich peptides (30-50 amino acids in size) and enzymes responsible for dehydration and cyclization, catalyzing the post-translational ring formation. One such identified, class I lantibiotic is maddinglicin from Clostridium maddingley. Here, we present single particle cryo-EM structures of the dehydratase MadB in both, its apo-state and in complex with a leader peptide of maddinglicin, revealing a distinct conformational change upon substrate binding. Small-angle X-ray scattering studies elucidate the substrate binding site for the C-terminal part of maddinglicin. Furthermore, a substrate specificity analysis was performed highlighting a critical stretch of amino acids within the maddinglicin leader sequence that is crucial for binding. Here, we provide molecular insights into the conformational changes, principles of substrate recognition and ligand:protein stoichiometry of a class I lantibiotic dehydratase. | |||||||
| Rechtliche Vermerke: | Originalveröffentlichung:
Knospe, C. V., Ortiz, J., Reiners, J., Kedrov, A., Gertzen, C. G. W., Smits, S. H. J., & Schmitt, L. (2025). Structural insights into the substrate binding mechanism of the class I dehydratase MadB. Communications Biology, 8, Article 1032. https://doi.org/10.1038/s42003-025-08454-5 | |||||||
| Lizenz: |  Dieses Werk ist lizenziert unter einer Creative Commons Namensnennung 4.0 International Lizenz | |||||||
| Fachbereich / Einrichtung: | Mathematisch- Naturwissenschaftliche Fakultät | |||||||
| Dokument erstellt am: | 18.07.2025 | |||||||
| Dateien geändert am: | 18.07.2025 |
