9SDW
tRNA (guanine-7-)-methyltransferase (trmD) from Staphylococcus aureus in complex with SAM-competitive compound
This is a non-PDB format compatible entry.
Summary for 9SDW
| Entry DOI | 10.2210/pdb9sdw/pdb |
| Descriptor | tRNA (guanine-N(1)-)-methyltransferase, 1-[2-[4-(4-oxidanylidene-3,7-dihydropyrrolo[2,3-d]pyrimidin-5-yl)-1,2,3-triazol-1-yl]ethyl]guanidine (3 entities in total) |
| Functional Keywords | trmd, inhibitor, m7g, s. aureus, transferase |
| Biological source | Staphylococcus aureus |
| Total number of polymer chains | 1 |
| Total formula weight | 30346.30 |
| Authors | Weldert, A.C.,Hof, F.,Huebner, A.F.,Wolf, E.,Barthels, F. (deposition date: 2025-08-14, release date: 2025-12-17, Last modification date: 2026-01-07) |
| Primary citation | Hubner, A.F.,Weldert, A.C.,Marciniak, T.,Hof, F.,Beck, V.S.,Carien, S.,Mulartschyk, S.N.,Wolf, E.,Ziebuhr, W.,Barthels, F. Nanoscale Direct-to-Biology Optimization and Structural Insights into Selective S. aureus TrmD Inhibitors. J.Med.Chem., 68:26246-26262, 2025 Cited by PubMed Abstract: The tRNA mG37 methyltransferase (TrmD) is considered essential in various bacteria, including , a pathogen responsible for a wide range of diseases. Here, we have performed a high-throughput nanomole-scale synthesis campaign (nanoSAR) by late-stage copper(I)-catalyzed alkyne-azide cycloaddition (CuAAC)-functionalizing a library of structurally diverse azides (N = 320) to a pyrrolopyrimidone alkyne. We have identified selective TrmD inhibitors with inhibitory activity in the nanomolar to low micromolar range using a direct-to-biology assay read-out. A carbamate-masked guanidine intermediate of the lead structure selectively inhibited growth at low micromolar concentrations in cell-based assays, while Gram-negative bacteria and an off-target panel of methyltransferases were not affected. Subsequent cocrystallization resulted in a crystal structure of TrmD bound to an inhibitor, providing detailed insights into its binding mode and enabling future structure-guided optimization. PubMed: 41367353DOI: 10.1021/acs.jmedchem.5c02323 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.6 Å) |
Structure validation
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