1n2v
From Proteopedia
(New page: 200px<br /><applet load="1n2v" size="450" color="white" frame="true" align="right" spinBox="true" caption="1n2v, resolution 2.1Å" /> '''Crystal Structure of ...) |
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| - | [[Image:1n2v.jpg|left|200px]]<br /><applet load="1n2v" size=" | + | [[Image:1n2v.jpg|left|200px]]<br /><applet load="1n2v" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1n2v, resolution 2.1Å" /> | caption="1n2v, resolution 2.1Å" /> | ||
'''Crystal Structure of TGT in complex with 2-Butyl-5,6-dihydro-1H-imidazo[4,5-d]pyridazine-4,7-dione'''<br /> | '''Crystal Structure of TGT in complex with 2-Butyl-5,6-dihydro-1H-imidazo[4,5-d]pyridazine-4,7-dione'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Eubacterial tRNA-guanine transglycosylase (TGT) is involved in the | + | Eubacterial tRNA-guanine transglycosylase (TGT) is involved in the hypermodification of cognate tRNAs, leading to the exchange of G34 by preQ1 at the wobble position in the anticodon loop. Mutation of the tgt gene in Shigella flexneri results in a significant loss of pathogenicity of the bacterium due to inefficient translation of a virulence protein mRNA. Herein, we describe the discovery of a ligand with an unexpected binding mode. On the basis of this binding mode, three slightly deviating pharmacophore hypotheses have been derived. Virtual screening based on this composite pharmacophore model retrieved a set of potential TGT inhibitors belonging to several compound classes. All nine tested inhibitors being representatives of these classes showed activity in the micromolar range, two of them even in the submicromolar range. |
==About this Structure== | ==About this Structure== | ||
| - | 1N2V is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Zymomonas_mobilis Zymomonas mobilis] with ZN and BDI as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Queuine_tRNA-ribosyltransferase Queuine tRNA-ribosyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.4.2.29 2.4.2.29] Full crystallographic information is available from [http:// | + | 1N2V is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Zymomonas_mobilis Zymomonas mobilis] with <scene name='pdbligand=ZN:'>ZN</scene> and <scene name='pdbligand=BDI:'>BDI</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Queuine_tRNA-ribosyltransferase Queuine tRNA-ribosyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.4.2.29 2.4.2.29] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1N2V OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Zymomonas mobilis]] | [[Category: Zymomonas mobilis]] | ||
[[Category: Brenk, R.]] | [[Category: Brenk, R.]] | ||
| - | [[Category: Garcia, G | + | [[Category: Garcia, G A.]] |
| - | [[Category: Gerber, H | + | [[Category: Gerber, H D.]] |
[[Category: Graedler, U.]] | [[Category: Graedler, U.]] | ||
[[Category: Klebe, G.]] | [[Category: Klebe, G.]] | ||
[[Category: Naerum, L.]] | [[Category: Naerum, L.]] | ||
[[Category: Reuter, K.]] | [[Category: Reuter, K.]] | ||
| - | [[Category: Stubbs, M | + | [[Category: Stubbs, M T.]] |
[[Category: BDI]] | [[Category: BDI]] | ||
[[Category: ZN]] | [[Category: ZN]] | ||
[[Category: protein-ligand complex]] | [[Category: protein-ligand complex]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:01:40 2008'' |
Revision as of 12:01, 21 February 2008
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Crystal Structure of TGT in complex with 2-Butyl-5,6-dihydro-1H-imidazo[4,5-d]pyridazine-4,7-dione
Overview
Eubacterial tRNA-guanine transglycosylase (TGT) is involved in the hypermodification of cognate tRNAs, leading to the exchange of G34 by preQ1 at the wobble position in the anticodon loop. Mutation of the tgt gene in Shigella flexneri results in a significant loss of pathogenicity of the bacterium due to inefficient translation of a virulence protein mRNA. Herein, we describe the discovery of a ligand with an unexpected binding mode. On the basis of this binding mode, three slightly deviating pharmacophore hypotheses have been derived. Virtual screening based on this composite pharmacophore model retrieved a set of potential TGT inhibitors belonging to several compound classes. All nine tested inhibitors being representatives of these classes showed activity in the micromolar range, two of them even in the submicromolar range.
About this Structure
1N2V is a Single protein structure of sequence from Zymomonas mobilis with and as ligands. Active as Queuine tRNA-ribosyltransferase, with EC number 2.4.2.29 Full crystallographic information is available from OCA.
Reference
Virtual screening for submicromolar leads of tRNA-guanine transglycosylase based on a new unexpected binding mode detected by crystal structure analysis., Brenk R, Naerum L, Gradler U, Gerber HD, Garcia GA, Reuter K, Stubbs MT, Klebe G, J Med Chem. 2003 Mar 27;46(7):1133-43. PMID:12646024
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