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| | <StructureSection load='3s1g' size='340' side='right'caption='[[3s1g]], [[Resolution|resolution]] 1.82Å' scene=''> | | <StructureSection load='3s1g' size='340' side='right'caption='[[3s1g]], [[Resolution|resolution]] 1.82Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3s1g]] is a 1 chain structure with sequence from [https://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=3S1G OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3S1G FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3s1g]] 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=3S1G OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3S1G FirstGlance]. <br> |
| - | </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=ITE:2-(METHYLAMINO)-1,7-DIHYDRO-8H-IMIDAZO[4,5-G]QUINAZOLIN-8-ONE'>ITE</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]] 1.82Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[2z7k|2z7k]], [[3eos|3eos]], [[3gev|3gev]], [[3gfn|3gfn]], [[3tll|3tll]], [[3v0y|3v0y]], [[3sm0|3sm0]], [[3rr4|3rr4]]</div></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=ITE:2-(METHYLAMINO)-1,7-DIHYDRO-8H-IMIDAZO[4,5-G]QUINAZOLIN-8-ONE'>ITE</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, ZMO0363 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=542 "Achromobacter anaerobium" (sic) Shimwell 1937])</td></tr> | + | |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/tRNA-guanine(34)_transglycosylase tRNA-guanine(34) transglycosylase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.4.2.29 2.4.2.29] </span></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=3s1g FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3s1g OCA], [https://pdbe.org/3s1g PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3s1g RCSB], [https://www.ebi.ac.uk/pdbsum/3s1g PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3s1g ProSAT]</span></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=3s1g FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3s1g OCA], [https://pdbe.org/3s1g PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3s1g RCSB], [https://www.ebi.ac.uk/pdbsum/3s1g PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3s1g ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == 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]
| + | [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] |
| - | <div style="background-color:#fffaf0;">
| + | |
| - | == Publication Abstract from PubMed ==
| + | |
| - | The foodborne illness shigellosis is caused by Shigella bacteria that secrete the highly cytotoxic Shiga toxin, which is also formed by the closely related enterohemorrhagic Escherichia coli (EHEC). It has been shown that tRNA-guanine transglycosylase (TGT) is essential for the pathogenicity of Shigella flexneri. Herein, the molecular recognition properties of a guanine binding pocket in Zymomonas mobilis TGT are investigated with a series of lin-benzohypoxanthine- and lin-benzoguanine-based inhibitors that bear substituents to occupy either the ribose-33 or the ribose-34 pocket. The three inhibitor scaffolds differ by the substituent at C(6) being H, NH(2) , or NHalkyl. These differences lead to major changes in the inhibition constants, pK(a) values, and binding modes. Compared to the lin-benzoguanines, with an exocyclic NH(2) at C(6), the lin-benzohypoxanthines without an exocyclic NH(2) group have a weaker affinity as several ionic protein-ligand hydrogen bonds are lost. X-ray cocrystal structure analysis reveals that a new water cluster is imported into the space vacated by the lacking NH(2) group and by a conformational shift of the side chain of catalytic Asp102. In the presence of an N-alkyl group at C(6) in lin-benzoguanine ligands, this water cluster is largely maintained but replacement of one of the water molecules in the cluster leads to a substantial loss in binding affinity. This study provides new insight into the role of water clusters at enzyme active sites and their challenging substitution by ligand parts, a topic of general interest in contemporary structure-based drug design.
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| - | | + | |
| - | From lin-Benzoguanines to lin-Benzohypoxanthines as Ligands for Zymomonas mobilis tRNA-Guanine Transglycosylase: Replacement of Protein-Ligand Hydrogen Bonding by Importing Water Clusters.,Barandun LJ, Immekus F, Kohler PC, Tonazzi S, Wagner B, Wendelspiess S, Ritschel T, Heine A, Kansy M, Klebe G, Diederich F Chemistry. 2012 Jun 26. doi: 10.1002/chem.201200809. PMID:22736391<ref>PMID:22736391</ref>
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| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
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| - | </div>
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| - | <div class="pdbe-citations 3s1g" style="background-color:#fffaf0;"></div>
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| | | | |
| | ==See Also== | | ==See Also== |
| | *[[TRNA-guanine transglycosylase 3D structures|TRNA-guanine transglycosylase 3D structures]] | | *[[TRNA-guanine transglycosylase 3D structures|TRNA-guanine transglycosylase 3D structures]] |
| - | == References == | |
| - | <references/> | |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Heine, A]] | + | [[Category: Zymomonas mobilis]] |
| - | [[Category: Immekus, F]] | + | [[Category: Heine A]] |
| - | [[Category: Klebe, G]] | + | [[Category: Immekus F]] |
| - | [[Category: Biosynthesis]] | + | [[Category: Klebe G]] |
| - | [[Category: Glycosyltransferase]]
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| - | [[Category: Metal-binding]]
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| - | [[Category: Queuosine]]
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| - | [[Category: Tim barrel]]
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| - | [[Category: Transferase]]
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| - | [[Category: Transferase-transferase inhibitor complex]]
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| - | [[Category: Trna]]
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| - | [[Category: Trna processing]]
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