9GDJ
C-Methyltransferase SgMT from Streptomyces griseoviridis
Summary for 9GDJ
| Entry DOI | 10.2210/pdb9gdj/pdb |
| Descriptor | Methyltransferase, COBALT HEXAMMINE(III), TRIETHYLENE GLYCOL, ... (8 entities in total) |
| Functional Keywords | methyl transfer, pyrroloindole synthesis, rossmann fold, s-adenosyl methionine, transferase |
| Biological source | Streptomyces griseoviridis |
| Total number of polymer chains | 3 |
| Total formula weight | 101339.27 |
| Authors | Weiergraeber, O.H.,Haase, M.,Pietruszka, J. (deposition date: 2024-08-05, release date: 2025-02-19, Last modification date: 2025-03-19) |
| Primary citation | Haase, M.,Weiergraber, O.H.,David, B.,Pfirmann, E.L.,Paschold, B.,Gohlke, H.,Pietruszka, J. Characterization of a C-methyltransferase from Streptomyces griseoviridis - crystal structure, mechanism, and substrate scope. Chem Sci, 16:4519-4527, 2025 Cited by PubMed Abstract: 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 . 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-()-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. PubMed: 39926702DOI: 10.1039/d4sc07300b PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.47 Å) |
Structure validation
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