Catalogo Articoli (Spogli Riviste)

OPAC HELP

Titolo:
A new target for shigellosis: Rational design and crystallographic studiesof inhibitors of tRNA-guanine transglycosylase
Autore:
Gradler, U; Gerber, HD; Goodenough-Lashua, DM; Garcia, GA; Ficner, R; Reuter, K; Stubbs, MT; Klebe, G;
Indirizzi:
Univ Marburg, Inst Pharmazeut Chem, D-35032 Marburg, Germany Univ MarburgMarburg Germany D-35032 zeut Chem, D-35032 Marburg, Germany Univ Marburg, Inst Mol Biol & Tumorforsch, D-35037 Marburg, Germany Univ Marburg Marburg Germany D-35037 morforsch, D-35037 Marburg, Germany Univ Michigan, Coll Pharm, Interdept Program Med Chem, Ann Arbor, MI 48109USA Univ Michigan Ann Arbor MI USA 48109 ram Med Chem, Ann Arbor, MI 48109USA
Titolo Testata:
JOURNAL OF MOLECULAR BIOLOGY
fascicolo: 3, volume: 306, anno: 2001,
pagine: 455 - 467
SICI:
0022-2836(20010223)306:3<455:ANTFSR>2.0.ZU;2-T
Fonte:
ISI
Lingua:
ENG
Soggetto:
DE-NOVO DESIGN; TRANSFER-RNA; ESCHERICHIA-COLI; ZYMOMONAS-MOBILIS; PROTEIN LIGANDS; ENZYME; GENE; VIRULENCE; FLEXNERI; BIOSYNTHESIS;
Keywords:
rational drug design; Shigellosis; modified tRNA nucleoside; LUDI; crystal structure;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
37
Recensione:
Indirizzi per estratti:
Indirizzo: Klebe, G Univ Marburg, Inst Pharmazeut Chem, Marbacher Weg 6, D-35032 Marburg, Germany Univ Marburg Marbacher Weg 6 Marburg Germany D-35032 rg, Germany
Citazione:
U. Gradler et al., "A new target for shigellosis: Rational design and crystallographic studiesof inhibitors of tRNA-guanine transglycosylase", J MOL BIOL, 306(3), 2001, pp. 455-467

Abstract

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 preQ(1) (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 struc ture of Zymomonas mobilis TGT in complex with preQ(1) 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 Angstrom crystal structure of APH in complex with Z. mobilis TGT served as a starting point for further modification of this initial lead. (C) 2001 Academic Press.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 03/04/20 alle ore 14:25:32