1q66
From Proteopedia
(New page: 200px<br /><applet load="1q66" size="450" color="white" frame="true" align="right" spinBox="true" caption="1q66, resolution 1.75Å" /> '''CRYSTAL STRUCTURE OF...) |
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| - | [[Image:1q66.gif|left|200px]]<br /><applet load="1q66" size=" | + | [[Image:1q66.gif|left|200px]]<br /><applet load="1q66" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1q66, resolution 1.75Å" /> | caption="1q66, resolution 1.75Å" /> | ||
'''CRYSTAL STRUCTURE OF TGT IN COMPLEX WITH 2-AMINO-6-AMINOMETHYL-8-phenylsulfanylmethyl-3H-QUINAZOLIN-4-ONE crystallized at pH 5.5'''<br /> | '''CRYSTAL STRUCTURE OF TGT IN COMPLEX WITH 2-AMINO-6-AMINOMETHYL-8-phenylsulfanylmethyl-3H-QUINAZOLIN-4-ONE crystallized at pH 5.5'''<br /> | ||
==Overview== | ==Overview== | ||
| - | The enzyme tRNA-guanine transglycosylase (TGT) is involved in the | + | The enzyme tRNA-guanine transglycosylase (TGT) is involved in the pathogenicity of Shigellae. As the crystal structure of this protein is known, it is a putative target for the structure-based design of inhibitors. Here we report a crystallographic study of several new ligands exhibiting a 2,6-diamino-3H-quinazolin-4-one scaffold, which has been shown recently to be a promising template for TGT-inhibitors. Crystal structure analysis of these complexes has revealed an unexpected movement of the side-chain of Asp102. A detailed analysis of the water network disrupted by this rotation has lead to the derivation of a new composite pharmacophore. A virtual screening has been performed based on this pharmacophore hypothesis and several new inhibitors of micromolar binding affinity with new skeletons have been discovered. |
==About this Structure== | ==About this Structure== | ||
| - | 1Q66 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 KMB 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:// | + | 1Q66 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=KMB:'>KMB</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=1Q66 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: Klebe, G.]] | [[Category: Klebe, G.]] | ||
[[Category: Meyer, E.]] | [[Category: Meyer, E.]] | ||
[[Category: Reuter, K.]] | [[Category: Reuter, K.]] | ||
| - | [[Category: Stubbs, M | + | [[Category: Stubbs, M T.]] |
[[Category: KMB]] | [[Category: KMB]] | ||
[[Category: ZN]] | [[Category: ZN]] | ||
[[Category: transferase]] | [[Category: transferase]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:36:15 2008'' |
Revision as of 12:36, 21 February 2008
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CRYSTAL STRUCTURE OF TGT IN COMPLEX WITH 2-AMINO-6-AMINOMETHYL-8-phenylsulfanylmethyl-3H-QUINAZOLIN-4-ONE crystallized at pH 5.5
Overview
The enzyme tRNA-guanine transglycosylase (TGT) is involved in the pathogenicity of Shigellae. As the crystal structure of this protein is known, it is a putative target for the structure-based design of inhibitors. Here we report a crystallographic study of several new ligands exhibiting a 2,6-diamino-3H-quinazolin-4-one scaffold, which has been shown recently to be a promising template for TGT-inhibitors. Crystal structure analysis of these complexes has revealed an unexpected movement of the side-chain of Asp102. A detailed analysis of the water network disrupted by this rotation has lead to the derivation of a new composite pharmacophore. A virtual screening has been performed based on this pharmacophore hypothesis and several new inhibitors of micromolar binding affinity with new skeletons have been discovered.
About this Structure
1Q66 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
Crystallographic study of inhibitors of tRNA-guanine transglycosylase suggests a new structure-based pharmacophore for virtual screening., Brenk R, Meyer EA, Reuter K, Stubbs MT, Garcia GA, Diederich F, Klebe G, J Mol Biol. 2004 Apr 16;338(1):55-75. PMID:15050823
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