The complex of a designer antibiotic with a model aminoacyl site of the 30S ribosomal subunit revealed by X-ray crystallography

被引：63

作者：

Russell, RJM

Murray, JB

Lentzen, G

Haddad, J

Mobashery, S

机构：

[1] RiboTargets, Cambridge CB1 6GB, England

[2] Wayne State Univ, Dept Chem, Detroit, MI 48202 USA

来源：

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY | 2003年 / 125卷 / 12期

关键词：

D O I：

10.1021/ja029736h

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

The ribosome is an important target for aminoglycoside antibiotics; however, the clinical effectiveness of aminoglycosides has diminished due to bacterial resistance mechanisms. Here we report the X-ray structure of a novel synthetic aminoglycoside bound to the A site of the ribosome, its target for manifestation of activity. The structure validates the in silico design paradigms for the antibiotic and reveals the molecular interactions made by this novel antibiotic in prokaryotes. Copyright © 2003 American Chemical Society.

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页码：3410 / 3411

页数：2

相关论文

共 11 条

[1]

[Anonymous], ACTA CRYSTALLOGR D

[2] Crystallography & NMR system:: A new software suite for macromolecular structure determination [J].

Brunger, AT ;

Adams, PD ;

Clore, GM ;

DeLano, WL ;

Gros, P ;

Grosse-Kunstleve, RW ;

Jiang, JS ;

Kuszewski, J ;

Nilges, M ;

Pannu, NS ;

Read, RJ ;

Rice, LM ;

Simonson, T ;

Warren, GL .

ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY, 1998, 54 :905-921

[3]

Delano WL, 2002, PYMOL USERS MANUAL

[4] Substrate promiscuity of an aminoglycoside antibiotic resistance enzyme via target mimicry [J].

Fong, DH ;

Berghuis, AM .

EMBO JOURNAL, 2002, 21 (10) :2323-2331

[5] Design of novel antibiotics that bind to the ribosomal acyltransfer site [J].

Haddad, J ;

Kotra, LP ;

Llano-Sotelo, B ;

Kim, C ;

Azucena, EF ;

Liu, MZ ;

Vakulenko, SB ;

Chow, CS ;

Mobashery, S .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2002, 124 (13) :3229-3237

[6] The bacterial ribosome, a promising focus for structure-based drug design [J].

Knowles, DJC ;

Foloppe, N ;

Matassova, NB ;

Murchie, AIH .

CURRENT OPINION IN PHARMACOLOGY, 2002, 2 (05) :501-506

[7] Recognition of cognate transfer RNA by the 30S ribosomal subunit [J].

Ogle, JM ;

Brodersen, DE ;

Clemons, WM ;

Tarry, MJ ;

Carter, AP ;

Ramakrishnan, V .

SCIENCE, 2001, 292 (5518) :897-902

[8] Processing of X-ray diffraction data collected in oscillation mode [J].

Otwinowski, Z ;

Minor, W .

MACROMOLECULAR CRYSTALLOGRAPHY, PT A, 1997, 276 :307-326

[9] Ribosome structure and the mechanism of translation [J].

Ramakrishnan, V .

CELL, 2002, 108 (04) :557-572

[10] Crystal structure of paromomycin docked into the eubacterial ribosomal decoding a site [J].

Vicens, Q ;

Westhof, E .

STRUCTURE, 2001, 9 (08) :647-658