View source for 6fmn


==tRNA guanine Transglycosylase (TGT) in co-crystallized complex with 6-amino-2-((((2R,3S,4R,5R)-3,4-dihydroxy-5-methoxytetrahydrofuran-2-yl)methyl)amino)-1,7-dihydro-8H-imidazo[4,5-g]quinazolin-8-one==
<StructureSection load='6fmn' size='340' side='right'caption='[[6fmn]], [[Resolution|resolution]] 1.36&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6fmn]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6FMN OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6FMN FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=E4E:6-azanyl-2-[[(2~{R},3~{S},4~{R},5~{R})-5-methoxy-3,4-bis(oxidanyl)oxolan-2-yl]methylamino]-3,7-dihydroimidazo[4,5-g]quinazolin-8-one'>E4E</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5jsv|5jsv]]</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=6fmn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6fmn OCA], [http://pdbe.org/6fmn PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6fmn RCSB], [http://www.ebi.ac.uk/pdbsum/6fmn PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6fmn ProSAT]</span></td></tr>
</table>
== 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] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The intestinal disease shigellosis caused by Shigella bacteria affects over 120 million people annually. There is an urgent demand for new drugs as resistance against common antibiotics emerges. Bacterial tRNA-guanine transglycosylase (TGT) is a druggable target and controls the pathogenicity of Shigella flexneri. We report the synthesis of sugar-functionalized lin-benzoguanines addressing the ribose-33 pocket of TGT from Zymomonas mobilis. Ligand binding was analyzed by isothermal titration calorimetry and X-ray crystallography. Pocket occupancy was optimized by variation of size and protective groups of the sugars. The participation of a polycyclic water-cluster in the recognition of the sugar moiety was revealed. Acetonide-protected ribo- and psicofuranosyl derivatives are highly potent, benefiting from structural rigidity, good solubility, and metabolic stability. We conclude that sugar acetonides have a significant but not yet broadly recognized value in drug development.

Sugar Acetonides are a Superior Motif for Addressing the Large, Solvent-Exposed Ribose-33 Pocket of tRNA-Guanine Transglycosylase.,Movsisyan LD, Schafer E, Nguyen A, Ehrmann FR, Schwab A, Rossolini T, Zimmerli D, Wagner B, Daff H, Heine A, Klebe G, Diederich F Chemistry. 2018 Jul 11;24(39):9957-9967. doi: 10.1002/chem.201801756. Epub 2018, Jun 25. PMID:29939431<ref>PMID:29939431</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6fmn" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Heine, A]]
[[Category: Klebe, G]]
[[Category: Nguyen, A]]
[[Category: Carbohydrate]]
[[Category: Co-crystallization]]
[[Category: Transferase]]
[[Category: Transferase inhibitor]]