Dokument: Characterization of a C-methyltransferase from Streptomyces griseoviridis – crystal structure, mechanism, and substrate scope
| Titel: | Characterization of a C-methyltransferase from Streptomyces griseoviridis – crystal structure, mechanism, and substrate scope | |||||||
| URL für Lesezeichen: | https://docserv.uni-duesseldorf.de/servlets/DocumentServlet?id=72794 | |||||||
| URN (NBN): | urn:nbn:de:hbz:061-20260401-120333-7 | |||||||
| Kollektion: | Publikationen | |||||||
| Sprache: | Englisch | |||||||
| Dokumententyp: | Wissenschaftliche Texte » Artikel, Aufsatz | |||||||
| Medientyp: | Text | |||||||
| Autoren: | Haase, Mona [Autor] Pfirmann, Elias L. [Autor] Paschold, Beatrix [Autor] Gohlke, Holger [Autor] Pietruszka, Jörg [Autor] Weiergräber, Oliver H. [Autor] David, Benoit [Autor] | |||||||
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| Beschreibung: | Despite the presence of pyrroloindoles in many natural products with diverse biological activities, their synthesis remains challenging in terms of stereoselectivity, especially with respect to methylation at the indole C3 position. In the present study, the pyrroloindole motif in tryptophan-based diketopiperazines (DKPs) is synthesized using the SAM-dependent methyltransferase SgMT from Streptomyces griseoviridis. The three-dimensional structure of this indole C3-methyltransferase was determined by X-ray crystallography, providing insights into the enzyme. The complex active site was explored by site-directed mutagenesis, highlighting an intriguing network of tyrosine side chains that is involved in catalytic activity. The enzyme's precise substrate requirements were characterized using a broad panel of methylation educts, while molecular docking and molecular dynamics simulations revealed the catalytic binding mode of the cyclo-(LL)-ditryptophan substrate. This study provides an in-depth account of the structure and catalytic properties of SgMT, which may apply to other diketopiperazine-targeting indole C3-methyltransferases, thus paving the way for their optimization as biocatalysts. | |||||||
| Rechtliche Vermerke: | Originalveröffentlichung:
Haase, M., Weiergräber, O. H., David, B., Pfirmann, E. L., Paschold, B., Gohlke, H., & Pietruszka, J. (2025). Characterization of a C-methyltransferase from Streptomyces griseoviridis – crystal structure, mechanism, and substrate scope. Chemical Science, 16(10), 4519–4527. https://doi.org/10.1039/d4sc07300b | |||||||
| Lizenz: |  Dieses Werk ist lizenziert unter einer Creative Commons Namensnennung 4.0 International Lizenz | |||||||
| Fachbereich / Einrichtung: | Mathematisch- Naturwissenschaftliche Fakultät | |||||||
| Dokument erstellt am: | 01.04.2026 | |||||||
| Dateien geändert am: | 01.04.2026 |
