View source for 5uti


==Crystal Structure of TGT in complex with fragment in preQ1 pocket==
<StructureSection load='5uti' size='340' side='right'caption='[[5uti]], [[Resolution|resolution]] 1.36&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5uti]] 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=5UTI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5UTI 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]] 1.36&#8491;</td></tr>
<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=GGB:L-CANAVANINE'>GGB</scene>, <scene name='pdbligand=PG4:TETRAETHYLENE+GLYCOL'>PG4</scene>, <scene name='pdbligand=PGE:TRIETHYLENE+GLYCOL'>PGE</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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=5uti FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5uti OCA], [https://pdbe.org/5uti PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5uti RCSB], [https://www.ebi.ac.uk/pdbsum/5uti PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5uti ProSAT]</span></td></tr>
</table>
== Function ==
[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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== Publication Abstract from PubMed ==
Crystallography provides structural information crucial for fragment optimization, however several criteria must be met to screen directly on protein crystals as soakable, well-diffracting specimen must be available. We screened a 96-fragment library against the tRNA-modifying enzyme TGT using crystallography. Eight hits, some with surprising binding poses, were detected. However, the amount of data collection, reduction and refinement is assumed substantial. Therefore, having a reliable cascade of fast and cost-efficient methods available for pre-screening before embarking to elaborate crystallographic screening appears beneficial. This allows filtering of compounds to the most promising hits, available to rapidly progress from hit-to-lead. But how to ensure that this workflow is reliable? To answer this question, we also applied SPR and NMR to the same screening sample to study whether identical hits are retrieved. Upon hit-list comparisons, crystallography shows with NMR and SPR, only one overlapping hit and all three methods shared no common hits. This questions a cascade-type screening protocol at least in the current example. Compared to crystallography, SPR and NMR detected higher percentages of non-active-site binders suggesting the importance of running reporter ligand-based competitive screens in SPR and NMR, a requirement not needed in crystallography. Although not specific, NMR proved a more sensitive method relative to SPR and crystallography, as it picked up the highest numbers of binders.

Fragments as Novel Starting Points for tRNA-Guanine Transglycosylase Inhibitors Found by Alternative Screening Strategies.,Hassaan E, Eriksson PO, Geschwindner S, Heine A, Klebe G ChemMedChem. 2020 Feb 5;15(3):324-337. doi: 10.1002/cmdc.201900604. Epub 2020 Jan, 29. PMID:31808981<ref>PMID:31808981</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 5uti" style="background-color:#fffaf0;"></div>

==See Also==
*[[TRNA-guanine transglycosylase 3D structures|TRNA-guanine transglycosylase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Zymomonas mobilis subsp. mobilis ZM4 = ATCC 31821]]
[[Category: Hassaan E]]
[[Category: Heine A]]
[[Category: Klebe G]]