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==tRNA-guanine transglycosylase in complex with 6-amino-4-(2-hydroxyethyl)-2-(methylamino)-3,7-dihydro-8H-imidazo[4,5-g]quinazolin-8-one==
==tRNA-guanine transglycosylase in complex with 6-amino-4-(2-hydroxyethyl)-2-(methylamino)-3,7-dihydro-8H-imidazo[4,5-g]quinazolin-8-one==
<StructureSection load='3eou' size='340' side='right' caption='[[3eou]], [[Resolution|resolution]] 1.93&Aring;' scene=''>
<StructureSection load='3eou' size='340' side='right'caption='[[3eou]], [[Resolution|resolution]] 1.93&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[3eou]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/"achromobacter_anaerobium"_(sic)_shimwell_1937 "achromobacter anaerobium" (sic) shimwell 1937]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3EOU OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3EOU FirstGlance]. <br>
<table><tr><td colspan='2'>[[3eou]] 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=3EOU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3EOU FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=PK3:6-AMINO-4-(2-HYDROXYETHYL)-2-(METHYLAMINO)-3,7-DIHYDRO-8H-IMIDAZO[4,5-G]QUINAZOLIN-8-ONE'>PK3</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
</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='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3eos|3eos]], [[3c2n|3c2n]]</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=PK3:6-AMINO-4-(2-HYDROXYETHYL)-2-(METHYLAMINO)-3,7-DIHYDRO-8H-IMIDAZO[4,5-G]QUINAZOLIN-8-ONE'>PK3</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">TGT ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=542 "Achromobacter anaerobium" (sic) Shimwell 1937])</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=3eou FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3eou OCA], [https://pdbe.org/3eou PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3eou RCSB], [https://www.ebi.ac.uk/pdbsum/3eou PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3eou ProSAT]</span></td></tr>
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/tRNA-guanine(34)_transglycosylase tRNA-guanine(34) transglycosylase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.4.2.29 2.4.2.29] </span></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3eou FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3eou OCA], [http://pdbe.org/3eou PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3eou RCSB], [http://www.ebi.ac.uk/pdbsum/3eou PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3eou ProSAT]</span></td></tr>
</table>
</table>
== Function ==
== Function ==
[[http://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]  
[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 ==
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
[[Image:Consurf_key_small.gif|200px|right]]
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</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=3eou ConSurf].
</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=3eou ConSurf].
<div style="clear:both"></div>
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
In a computational and structural study, we investigated a series of 4-substituted lin-benzoguanines that are potent inhibitors of tRNA-guanine transglycosylase (TGT), a putative target for the treatment of shigellosis. At first glance, it appears self-evident that the placement of a positively charged ligand functional group between the carboxylate groups of two adjacent aspartate residues in the glycosylase catalytic center leads to enhanced ligand binding. The concomitant displacement of water molecules that partially solvate the aspartates prior to ligand binding appears to result as a consequence of this. However, the case study presented herein shows that this premise is much too superficial. Placement of a likely positively charged amino group at such a pivotal position, interfering with the residual water solvation shell, is at best cost-neutral compared with the unsubstituted parent ligand not conflicting with the residual water shell. A ligand that orients a hydroxy group in this position shows even decreased binding. Based on the cost-neutral placement of the amino functionality, hydrophobic side chains can now be further attached to fill, with increasing potency, a small hydrophobic pocket remote to the aspartates. Any attempts to cross the pivotal position between both aspartates with nonpolar scaffolds reveals only decreased binding, even though the waters of the residual solvation shell are successfully repelled. This surprising observation fostered a detailed analysis of the role of water molecules involved in the residual solvation of polar active site residues. Their geometry and putative replacement in the binding pocket of TGT has been studied by a comparative database analysis, computational active site mapping, and a series of crystal structure analyses. Furthermore, conformational preferences of attached hydrophobic moieties explain their contribution to a gradual increase in binding affinity.
How to Replace the Residual Solvation Shell of Polar Active Site Residues to Achieve Nanomolar Inhibition of tRNA-Guanine Transglycosylase.,Ritschel T, Kohler PC, Neudert G, Heine A, Diederich F, Klebe G ChemMedChem. 2009 Dec;4(12):2012-23. PMID:19894214<ref>PMID:19894214</ref>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 3eou" style="background-color:#fffaf0;"></div>


==See Also==
==See Also==
*[[TRNA-guanine transglycosylase|TRNA-guanine transglycosylase]]
*[[TRNA-guanine transglycosylase 3D structures|TRNA-guanine transglycosylase 3D structures]]
== References ==
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Heine, A]]
[[Category: Large Structures]]
[[Category: Klebe, G]]
[[Category: Zymomonas mobilis]]
[[Category: Ritschel, T]]
[[Category: Heine A]]
[[Category: Glycosyltransferase]]
[[Category: Klebe G]]
[[Category: Metal-binding]]
[[Category: Ritschel T]]
[[Category: Queuosine biosynthesis]]
[[Category: Tim barrel]]
[[Category: Transferase]]
[[Category: Trna processing]]

Latest revision as of 08:25, 20 March 2024

tRNA-guanine transglycosylase in complex with 6-amino-4-(2-hydroxyethyl)-2-(methylamino)-3,7-dihydro-8H-imidazo[4,5-g]quinazolin-8-one

3eou, resolution 1.93Å

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