1f3e

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[[Image:1f3e.jpg|left|200px]]
 
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==A NEW TARGET FOR SHIGELLOSIS: RATIONAL DESIGN AND CRYSTALLOGRAPHIC STUDIES OF INHIBITORS OF TRNA-GUANINE TRANSGLYCOSYLASE==
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The line below this paragraph, containing "STRUCTURE_1f3e", creates the "Structure Box" on the page.
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<StructureSection load='1f3e' size='340' side='right'caption='[[1f3e]], [[Resolution|resolution]] 1.85&Aring;' scene=''>
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You may change the PDB parameter (which sets the PDB file loaded into the applet)
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== Structural highlights ==
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or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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<table><tr><td colspan='2'>[[1f3e]] 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=1F3E OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1F3E FirstGlance]. <br>
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or leave the SCENE parameter empty for the default display.
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.85&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DPZ:3,5-DIAMINOPHTHALHYDRAZIDE'>DPZ</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
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{{STRUCTURE_1f3e| PDB=1f3e | SCENE= }}
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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=1f3e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1f3e OCA], [https://pdbe.org/1f3e PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1f3e RCSB], [https://www.ebi.ac.uk/pdbsum/1f3e PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1f3e ProSAT]</span></td></tr>
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</table>
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== Function ==
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[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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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/f3/1f3e_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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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=1f3e ConSurf].
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<div style="clear:both"></div>
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'''A NEW TARGET FOR SHIGELLOSIS: RATIONAL DESIGN AND CRYSTALLOGRAPHIC STUDIES OF INHIBITORS OF TRNA-GUANINE TRANSGLYCOSYLASE'''
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==See Also==
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*[[TRNA-guanine transglycosylase 3D structures|TRNA-guanine transglycosylase 3D structures]]
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__TOC__
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==Overview==
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</StructureSection>
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Eubacterial tRNA-guanine transglycosylase (TGT) is involved in the hyper-modification of cognate tRNAs leading to the exchange of G34 at the wobble position in the anticodon loop by preQ1 (2-amino-5-(aminomethyl)pyrrolo[2,3-d]pyrimidin-4(3H)-one) as part of the biosynthesis of queuine (Q). Mutation of the tgt gene in Shigella flexneri results in a significant loss of pathogenicity of the bacterium, revealing TGT as a new target for the design of potent drugs against Shigellosis. The X-ray structure of Zymomonas mobilis TGT in complex with preQ1 was used to search for new putative inhibitors with the computer program LUDI. An initial screen of the Available Chemical Directory, a database compiled from commercially available compounds, suggested several hits. Of these, 4-aminophthalhydrazide (APH) showed an inhibition constant in the low micromolar range. The 1.95 A crystal structure of APH in complex with Z. mobilis TGT served as a starting point for further modification of this initial lead.
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[[Category: Large Structures]]
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==About this Structure==
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1F3E 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=1F3E OCA].
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==Reference==
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A new target for shigellosis: rational design and crystallographic studies of inhibitors of tRNA-guanine transglycosylase., Gradler U, Gerber HD, Goodenough-Lashua DM, Garcia GA, Ficner R, Reuter K, Stubbs MT, Klebe G, J Mol Biol. 2001 Feb 23;306(3):455-67. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/11178905 11178905]
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[[Category: Queuine tRNA-ribosyltransferase]]
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[[Category: Single protein]]
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[[Category: Zymomonas mobilis]]
[[Category: Zymomonas mobilis]]
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[[Category: Ficner, R.]]
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[[Category: Ficner R]]
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[[Category: Garcia, G A.G.]]
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[[Category: Garcia GAG]]
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[[Category: Gerber, H D.]]
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[[Category: Gerber H-D]]
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[[Category: Goodenough-Lashua, D M.]]
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[[Category: Goodenough-Lashua DM]]
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[[Category: Graedler, U.]]
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[[Category: Graedler U]]
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[[Category: Klebe, G.]]
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[[Category: Klebe G]]
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[[Category: Reuter, K.]]
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[[Category: Reuter K]]
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[[Category: Stubbs, M T.]]
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[[Category: Stubbs MT]]
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[[Category: Glycosyltransferase]]
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[[Category: Trna-modifying enzyme]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 15:50:44 2008''
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Current revision

A NEW TARGET FOR SHIGELLOSIS: RATIONAL DESIGN AND CRYSTALLOGRAPHIC STUDIES OF INHIBITORS OF TRNA-GUANINE TRANSGLYCOSYLASE

PDB ID 1f3e

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