1q66: Difference between revisions

Revision as of 15:36, 21 February 2008

CRYSTAL STRUCTURE OF TGT IN COMPLEX WITH 2-AMINO-6-AMINOMETHYL-8-phenylsulfanylmethyl-3H-QUINAZOLIN-4-ONE crystallized at pH 5.5

OverviewOverview

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 StructureAbout 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.

ReferenceReference

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

Page seeded by OCA on Thu Feb 21 14:36:15 2008

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OCA

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-[[Image:1q66.gif|left|200px]]<br /><applet load="1q66" size="450" color="white" frame="true" align="right" spinBox="true"
+[[Image:1q66.gif|left|200px]]<br /><applet load="1q66" size="350" color="white" frame="true" align="right" spinBox="true"
 caption="1q66, resolution 1.75&Aring;" />
 '''CRYSTAL STRUCTURE OF TGT IN COMPLEX WITH 2-AMINO-6-AMINOMETHYL-8-phenylsulfanylmethyl-3H-QUINAZOLIN-4-ONE crystallized at pH 5.5'''<br />
 ==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.
+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==
-Q66 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://ispc.weizmann.ac.il/oca-bin/ocashort?id=1Q66 OCA].
+Q66 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==
@@ Line 15: / Line 15: @@
 [[Category: Zymomonas mobilis]]
 [[Category: Brenk, R.]]
-[[Category: Garcia, G.A.]]
+[[Category: Garcia, G A.]]
 [[Category: Klebe, G.]]
 [[Category: Meyer, E.]]
 [[Category: Reuter, K.]]
-[[Category: Stubbs, M.T.]]
+[[Category: Stubbs, M T.]]
 [[Category: KMB]]
 [[Category: ZN]]
 [[Category: transferase]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Wed Nov 21 00:25:04 2007''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:36:15 2008''