1f3e: Difference between revisions

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[[Image:1f3e.jpg|left|200px]]
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{{STRUCTURE_1f3e|  PDB=1f3e  |  SCENE=  }}  
{{STRUCTURE_1f3e|  PDB=1f3e  |  SCENE=  }}  


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




==Overview==
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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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{{ABSTRACT_PUBMED_11178905}}


==About this Structure==
==About this Structure==
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[[Category: Glycosyltransferase]]
[[Category: Glycosyltransferase]]
[[Category: Trna-modifying enzyme]]
[[Category: Trna-modifying enzyme]]
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 15:50:44 2008''
 
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 1 02:36:19 2008''

Revision as of 23:36, 30 June 2008

File:1f3e.png

Template:STRUCTURE 1f3e

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

Template:ABSTRACT PUBMED 11178905

About this Structure

1F3E is a Single protein structure of sequence from Zymomonas mobilis. Full crystallographic information is available from OCA.

Reference

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:11178905

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