6rkq

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'''Unreleased structure'''
 
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The entry 6rkq is ON HOLD until Paper Publication
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==Crystal Structure of TGT in complex with N2-methyl-8-(prop-1-yn-1-yl)-3H,7H,8H-imidazo[4,5-g]quinazoline-2,6-diamine==
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<StructureSection load='6rkq' size='340' side='right'caption='[[6rkq]], [[Resolution|resolution]] 1.67&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[6rkq]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Zymomonas_mobilis_subsp._mobilis_ZM4_=_ATCC_31821 Zymomonas mobilis subsp. mobilis ZM4 = ATCC 31821]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6RKQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6RKQ FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.665&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=K75:(8~{R})-~{N}2-methyl-8-prop-1-ynyl-7,8-dihydro-3~{H}-imidazo[4,5-g]quinazoline-2,6-diamine'>K75</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6rkq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6rkq OCA], [https://pdbe.org/6rkq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6rkq RCSB], [https://www.ebi.ac.uk/pdbsum/6rkq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6rkq ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/TGT_ZYMMO TGT_ZYMMO] Exchanges the guanine residue with 7-aminomethyl-7-deazaguanine in tRNAs with GU(N) anticodons (tRNA-Asp, -Asn, -His and -Tyr). After this exchange, a cyclopentendiol moiety is attached to the 7-aminomethyl group of 7-deazaguanine, resulting in the hypermodified nucleoside queuosine (Q) (7-(((4,5-cis-dihydroxy-2-cyclopenten-1-yl)amino)methyl)-7-deazaguanosine).[HAMAP-Rule:MF_00168]
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Fragment-based lead discovery was applied to tRNA-guanine transglycosylase, an enzyme modifying post-transcriptionally tRNAs in Shigella, the causative agent of shigellosis. TGT inhibition prevents translation of Shigella's virulence factor VirF, hence reducing pathogenicity. One discovered fragment opens a transient subpocket in the preQ1-recognition site by pushing back an aspartate residue. This step is associated with reorganization of further amino acids structurally transforming a loop adjacent to the recognition site by duplicating the volume of the preQ1-recognition pocket. We synthesized 6-carboxamido-, 6-hydrazido-, and 4-guanidino-benzimidazoles to target the opened pocket, including a dihydro-imidazoquinazoline with a propyn-1-yl exit vector pointing into the transient pocket and displacing a conserved water network. MD simulations and hydration-site analysis suggest water displacement to contribute favorably to ligand binding. A cysteine residue, exclusively present in bacterial TGTs, serves as gatekeeper of the transient subpocket. It becomes accessible upon pocket opening for selective covalent attachment of electrophilic ligands in eubacterial TGTs.
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Authors: Hassaan, E., Heine, A., Klebe, G.
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Fragment Screening Hit Draws Attention to a Novel Transient Pocket Adjacent to the Recognition Site of the tRNA-Modifying Enzyme TGT.,Hassaan E, Hohn C, Ehrmann FR, Goetzke FW, Movsisyan L, Hufner-Wulsdorf T, Sebastiani M, Hartsch A, Reuter K, Diederich F, Klebe G J Med Chem. 2020 Jul 9;63(13):6802-6820. doi: 10.1021/acs.jmedchem.0c00115. Epub , 2020 Jun 25. PMID:32515955<ref>PMID:32515955</ref>
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Description: Crystal Structure of TGT in complex with N2-methyl-8-(prop-1-yn-1-yl)-3H,7H,8H-imidazo[4,5-g]quinazoline-2,6-diamine
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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[[Category: Unreleased Structures]]
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</div>
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[[Category: Heine, A]]
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<div class="pdbe-citations 6rkq" style="background-color:#fffaf0;"></div>
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[[Category: Hassaan, E]]
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[[Category: Klebe, G]]
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==See Also==
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*[[TRNA-guanine transglycosylase 3D structures|TRNA-guanine transglycosylase 3D structures]]
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== References ==
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<references/>
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__TOC__
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</StructureSection>
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[[Category: Large Structures]]
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[[Category: Zymomonas mobilis subsp. mobilis ZM4 = ATCC 31821]]
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[[Category: Hassaan E]]
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[[Category: Heine A]]
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[[Category: Klebe G]]

Current revision

Crystal Structure of TGT in complex with N2-methyl-8-(prop-1-yn-1-yl)-3H,7H,8H-imidazo[4,5-g]quinazoline-2,6-diamine

PDB ID 6rkq

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