9sdv: Difference between revisions
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The | ==tRNA (guanine-7-)-methyltransferase (trmD) from Staphylococcus aureus in complex with SAM-competitive compound== | ||
<StructureSection load='9sdv' size='340' side='right'caption='[[9sdv]], [[Resolution|resolution]] 2.50Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[9sdv]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Staphylococcus_aureus Staphylococcus aureus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=9SDV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9SDV FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.5Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=21X:N-[4-(AMINOMETHYL)BENZYL]-4-OXO-3,4-DIHYDROTHIENO[2,3-D]PYRIMIDINE-5-CARBOXAMIDE'>21X</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=9sdv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9sdv OCA], [https://pdbe.org/9sdv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9sdv RCSB], [https://www.ebi.ac.uk/pdbsum/9sdv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9sdv ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/TRMD_STAAS TRMD_STAAS] Specifically methylates guanosine-37 in various tRNAs. | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The tRNA m(1)G37 methyltransferase (TrmD) is considered essential in various bacteria, including Staphylococcus aureus, 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 S. aureus 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 S. aureus 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 S. aureus TrmD bound to an inhibitor, providing detailed insights into its binding mode and enabling future structure-guided optimization. | |||
Nanoscale Direct-to-Biology Optimization and Structural Insights into Selective S. aureus TrmD Inhibitors.,Hubner AF, Weldert AC, Marciniak T, Hof F, Beck VS, Carien S, Mulartschyk SN, Wolf E, Ziebuhr W, Barthels F J Med Chem. 2025 Dec 10. doi: 10.1021/acs.jmedchem.5c02323. PMID:41367353<ref>PMID:41367353</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 9sdv" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Staphylococcus aureus]] | |||
[[Category: Barthels F]] | |||
[[Category: Hof F]] | |||
[[Category: Huebner AF]] | |||
[[Category: Weldert AC]] | |||
[[Category: Wolf E]] | |||
Latest revision as of 13:10, 17 December 2025
tRNA (guanine-7-)-methyltransferase (trmD) from Staphylococcus aureus in complex with SAM-competitive compound
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