8apt: Difference between revisions
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==Crystal Structure of H. influenzae TrmD in complex with Compound 13== | |||
<StructureSection load='8apt' size='340' side='right'caption='[[8apt]], [[Resolution|resolution]] 1.80Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[8apt]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Haemophilus_influenzae Haemophilus influenzae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8APT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8APT FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CIT:CITRIC+ACID'>CIT</scene>, <scene name='pdbligand=NN9:6-[[3-(aminomethyl)phenyl]methylamino]pyridine-3-carboxamide'>NN9</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=8apt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8apt OCA], [https://pdbe.org/8apt PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8apt RCSB], [https://www.ebi.ac.uk/pdbsum/8apt PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8apt ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/TRMD_HAEIG TRMD_HAEIG] Specifically methylates guanosine-37 in various tRNAs. | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The post-transcriptional modifier tRNA-(N(1)G37) methyltransferase (TrmD) has been proposed to be essential for growth in many Gram-negative and Gram-positive pathogens, however previously reported inhibitors show only weak antibacterial activity. In this work, optimisation of fragment hits resulted in compounds with low nanomolar TrmD inhibition incorporating features designed to enhance bacterial permeability and covering a range of physicochemical space. The resulting lack of significant antibacterial activity suggests that whilst TrmD is highly ligandable, its essentiality and druggability are called into question. | |||
Evaluating the druggability of TrmD, a potential antibacterial target, through design and microbiological profiling of a series of potent TrmD inhibitors.,Wilkinson AJ, Ooi N, Finlayson J, Lee VE, Lyth D, Maskew KS, Newman R, Orr D, Ansell K, Birchall K, Canning P, Coombs P, Fusani L, McIver E, Pisco J, Ireland PM, Jenkins C, Norville IH, Southern SJ, Cowan R, Hall G, Kettleborough C, Savage VJ, Cooper IR Bioorg Med Chem Lett. 2023 Jun 15;90:129331. doi: 10.1016/j.bmcl.2023.129331. , Epub 2023 May 13. PMID:37187252<ref>PMID:37187252</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: | <div class="pdbe-citations 8apt" style="background-color:#fffaf0;"></div> | ||
[[Category: | == References == | ||
[[Category: | <references/> | ||
__TOC__ | |||
</StructureSection> | |||
[[Category: Haemophilus influenzae]] | |||
[[Category: Large Structures]] | |||
[[Category: Carr MD]] | |||
[[Category: Cowan R]] | |||
[[Category: Hall G]] | |||
Revision as of 11:15, 14 June 2023
Crystal Structure of H. influenzae TrmD in complex with Compound 13Crystal Structure of H. influenzae TrmD in complex with Compound 13
Structural highlights
FunctionTRMD_HAEIG Specifically methylates guanosine-37 in various tRNAs. Publication Abstract from PubMedThe post-transcriptional modifier tRNA-(N(1)G37) methyltransferase (TrmD) has been proposed to be essential for growth in many Gram-negative and Gram-positive pathogens, however previously reported inhibitors show only weak antibacterial activity. In this work, optimisation of fragment hits resulted in compounds with low nanomolar TrmD inhibition incorporating features designed to enhance bacterial permeability and covering a range of physicochemical space. The resulting lack of significant antibacterial activity suggests that whilst TrmD is highly ligandable, its essentiality and druggability are called into question. Evaluating the druggability of TrmD, a potential antibacterial target, through design and microbiological profiling of a series of potent TrmD inhibitors.,Wilkinson AJ, Ooi N, Finlayson J, Lee VE, Lyth D, Maskew KS, Newman R, Orr D, Ansell K, Birchall K, Canning P, Coombs P, Fusani L, McIver E, Pisco J, Ireland PM, Jenkins C, Norville IH, Southern SJ, Cowan R, Hall G, Kettleborough C, Savage VJ, Cooper IR Bioorg Med Chem Lett. 2023 Jun 15;90:129331. doi: 10.1016/j.bmcl.2023.129331. , Epub 2023 May 13. PMID:37187252[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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