9sdw: Difference between revisions

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'''Unreleased structure'''


The entry 9sdw is ON HOLD  until Paper Publication
==tRNA (guanine-7-)-methyltransferase (trmD) from Staphylococcus aureus in complex with SAM-competitive compound==
<StructureSection load='9sdw' size='340' side='right'caption='[[9sdw]], [[Resolution|resolution]] 2.60&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[9sdw]] 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=9SDW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9SDW 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]] 2.6&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=A1JNG:1-[2-[4-(4-oxidanylidene-3,7-dihydropyrrolo[2,3-d]pyrimidin-5-yl)-1,2,3-triazol-1-yl]ethyl]guanidine'>A1JNG</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=9sdw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9sdw OCA], [https://pdbe.org/9sdw PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9sdw RCSB], [https://www.ebi.ac.uk/pdbsum/9sdw PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9sdw 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.


Authors:  
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>


Description:  
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
[[Category: Unreleased Structures]]
</div>
<div class="pdbe-citations 9sdw" 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]]
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