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[[Image:1q4w.jpg|left|200px]]
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{{STRUCTURE_1q4w|  PDB=1q4w  |  SCENE=  }}
'''CRYSTAL STRUCTURE OF TGT IN COMPLEX WITH 2,6-DIAMINO-3H-QUINAZOLIN-4-ONE'''


==CRYSTAL STRUCTURE OF TGT IN COMPLEX WITH 2,6-DIAMINO-3H-QUINAZOLIN-4-ONE==
<StructureSection load='1q4w' size='340' side='right'caption='[[1q4w]], [[Resolution|resolution]] 1.93&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1q4w]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Zymomonas_mobilis Zymomonas mobilis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1Q4W OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1Q4W 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]] 1.93&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DQU:2,6-DIAMINO-3H-QUINAZOLIN-4-ONE'>DQU</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=1q4w FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1q4w OCA], [https://pdbe.org/1q4w PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1q4w RCSB], [https://www.ebi.ac.uk/pdbsum/1q4w PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1q4w 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]
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/q4/1q4w_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1q4w ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The enzyme tRNA-guanine transglycosylase (TGT) is involved in the pathogenicity of Shigellae. As the crystal structure of this protein is known, it is a putative target for the structure-based design of inhibitors. Here we report a crystallographic study of several new ligands exhibiting a 2,6-diamino-3H-quinazolin-4-one scaffold, which has been shown recently to be a promising template for TGT-inhibitors. Crystal structure analysis of these complexes has revealed an unexpected movement of the side-chain of Asp102. A detailed analysis of the water network disrupted by this rotation has lead to the derivation of a new composite pharmacophore. A virtual screening has been performed based on this pharmacophore hypothesis and several new inhibitors of micromolar binding affinity with new skeletons have been discovered.


==Overview==
Crystallographic study of inhibitors of tRNA-guanine transglycosylase suggests a new structure-based pharmacophore for virtual screening.,Brenk R, Meyer EA, Reuter K, Stubbs MT, Garcia GA, Diederich F, Klebe G J Mol Biol. 2004 Apr 16;338(1):55-75. PMID:15050823<ref>PMID:15050823</ref>
The enzyme tRNA-guanine transglycosylase (TGT) is involved in the pathogenicity of Shigellae. As the crystal structure of this protein is known, it is a putative target for the structure-based design of inhibitors. Here we report a crystallographic study of several new ligands exhibiting a 2,6-diamino-3H-quinazolin-4-one scaffold, which has been shown recently to be a promising template for TGT-inhibitors. Crystal structure analysis of these complexes has revealed an unexpected movement of the side-chain of Asp102. A detailed analysis of the water network disrupted by this rotation has lead to the derivation of a new composite pharmacophore. A virtual screening has been performed based on this pharmacophore hypothesis and several new inhibitors of micromolar binding affinity with new skeletons have been discovered.


==About this Structure==
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
1Q4W is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Zymomonas_mobilis Zymomonas mobilis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1Q4W OCA].
</div>
<div class="pdbe-citations 1q4w" style="background-color:#fffaf0;"></div>


==Reference==
==See Also==
Crystallographic study of inhibitors of tRNA-guanine transglycosylase suggests a new structure-based pharmacophore for virtual screening., Brenk R, Meyer EA, Reuter K, Stubbs MT, Garcia GA, Diederich F, Klebe G, J Mol Biol. 2004 Apr 16;338(1):55-75. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/15050823 15050823]
*[[TRNA-guanine transglycosylase 3D structures|TRNA-guanine transglycosylase 3D structures]]
[[Category: Queuine tRNA-ribosyltransferase]]
== References ==
[[Category: Single protein]]
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Zymomonas mobilis]]
[[Category: Zymomonas mobilis]]
[[Category: Brenk, R.]]
[[Category: Brenk R]]
[[Category: Garcia, G A.]]
[[Category: Garcia GA]]
[[Category: Klebe, G.]]
[[Category: Klebe G]]
[[Category: Meyer, E.]]
[[Category: Meyer E]]
[[Category: Reuter, K.]]
[[Category: Reuter K]]
[[Category: Stubbs, M T.]]
[[Category: Stubbs MT]]
[[Category: Transferase]]
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May  3 05:52:09 2008''
Retrieved from "https://proteopedia.org/1q4w"