View source for 6qqy


==Crystal structure of TrmD, a tRNA-(N1G37) methyltransferase, from Mycobacterium abscessus in complex with inhibitor==
<StructureSection load='6qqy' size='340' side='right'caption='[[6qqy]], [[Resolution|resolution]] 1.49&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6qqy]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycobacteroides_abscessus Mycobacteroides abscessus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6QQY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6QQY 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]] 1.49&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=JD2:5-azanyl-3-[1-(pyridin-2-ylmethyl)indol-6-yl]-1~{H}-pyrazole-4-carbonitrile'>JD2</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=6qqy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6qqy OCA], [https://pdbe.org/6qqy PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6qqy RCSB], [https://www.ebi.ac.uk/pdbsum/6qqy PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6qqy ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/B1MDI3_MYCA9 B1MDI3_MYCA9] Specifically methylates guanosine-37 in various tRNAs.[HAMAP-Rule:MF_00605][RuleBase:RU003464][SAAS:SAAS00040552]
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Translational frameshift errors are often deleterious to the synthesis of functional proteins and could therefore be promoted therapeutically to kill bacteria. TrmD (tRNA-(N(1)G37) methyltransferase) is an essential tRNA modification enzyme in bacteria that prevents +1 errors in the reading frame during protein translation and represents an attractive potential target for the development of new antibiotics. Here, we describe the application of a structure-guided fragment-based drug discovery approach to the design of a new class of inhibitors against TrmD in Mycobacterium abscessus. Fragment library screening, followed by structure-guided chemical elaboration of hits, led to the rapid development of drug-like molecules with potent in vitro TrmD inhibitory activity. Several of these compounds exhibit activity against planktonic M. abscessus and M. tuberculosis as well as against intracellular M. abscessus and M. leprae, indicating their potential as the basis for a novel class of broad-spectrum mycobacterial drugs.

Fragment-based discovery of a new class of inhibitors targeting mycobacterial tRNA modification.,Thomas SE, Whitehouse AJ, Brown K, Burbaud S, Belardinelli JM, Sangen J, Lahiri R, Libardo MDJ, Gupta P, Malhotra S, Boshoff HIM, Jackson M, Abell C, Coyne AG, Blundell TL, Floto RA, Mendes V Nucleic Acids Res. 2020 Jun 30. pii: 5865065. doi: 10.1093/nar/gkaa539. PMID:32602532<ref>PMID:32602532</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6qqy" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Mycobacteroides abscessus]]
[[Category: Abell C]]
[[Category: Blundell TL]]
[[Category: Coyne AG]]
[[Category: Mendes V]]
[[Category: Thomas SE]]
[[Category: Whitehouse AJ]]