Structural highlights
Function
[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]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
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.
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[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Gradler U, Gerber HD, Goodenough-Lashua DM, Garcia GA, Ficner R, Reuter K, Stubbs MT, Klebe G. A new target for shigellosis: rational design and crystallographic studies of inhibitors of tRNA-guanine transglycosylase. J Mol Biol. 2001 Feb 23;306(3):455-67. PMID:11178905 doi:10.1006/jmbi.2000.4256
