View source for 6nvr


==Crystal structure of TrmD, a tRNA-(N1G37) methyltransferase, from Mycobacterium abscessus in Apo form==
<StructureSection load='6nvr' size='340' side='right'caption='[[6nvr]], [[Resolution|resolution]] 1.56&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6nvr]] 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=6NVR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6NVR 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]] 1.562&#8491;</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=6nvr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6nvr OCA], [https://pdbe.org/6nvr PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6nvr RCSB], [https://www.ebi.ac.uk/pdbsum/6nvr PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6nvr 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]
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== 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>
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==See Also==
*[[TRNA methyltransferase 3D structures|TRNA methyltransferase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Mycobacteroides abscessus]]
[[Category: Abell C]]
[[Category: Blundell TL]]
[[Category: Coyne AG]]
[[Category: Mendes VM]]
[[Category: Thomas SE]]
[[Category: Whitehouse AJ]]