Amicoumacin A Inhibits Translation by Stabilizing mRNA Interaction with the Ribosome

被引：71

作者：

Polikanov, Yury S. ^{[1
,2
]}

Osterman, Ilya A. ^{[3
,4
]}

Szal, Teresa ^{[5
]}

Tashlitsky, Vadim N. ^{[3
,4
]}

Serebryakova, Marina V. ^{[3
,4
]}

Kusochek, Pavel ^{[3
,4
]}

Bulkley, David ^{[1
]}

Malanicheva, Irina A. ^{[6
]}

Efimenko, Tatyana A. ^{[6
]}

Efremenkova, Olga V. ^{[6
]}

Konevega, Andrey L. ^{[7
,8
]}

Shaw, Karen J. ^{[9
]}

Bogdanov, Alexey A. ^{[3
,4
]}

Rodnina, Marina V. ^{[10
]}

Dontsova, Olga A. ^{[3
,4
]}

Mankin, Alexander S. ^{[5
]}

Steitz, Thomas A. ^{[1
,2
]}

Sergiev, Petr V. ^{[3
,4
]}

机构：

[1] Yale Univ, Dept Mol Biophys & Biochem, New Haven, CT 06520 USA

[2] Yale Univ, Howard Hughes Med Inst, New Haven, CT 06520 USA

[3] Moscow MV Lomonosov State Univ, Dept Chem, Moscow 119992, Russia

[4] AN Belozersky Inst Physicochem Biol, Moscow 119992, Russia

[5] Univ Illinois, Ctr Pharmaceut Biotechnol, Chicago, IL 60607 USA

[6] Russian Acad Med Sci, GF Gause Inst New Antibiot, Moscow 119867, Russia

[7] BP Konstantinov Petersburg Nucl Phys Inst, Gatchina 188300, Russia

[8] St Petersburg State Polytech Univ, St Petersburg 195251, Russia

[9] Hearts Consulting Grp, San Diego, CA 92127 USA

[10] Max Planck Inst Biophys Chem, D-37077 Gottingen, Germany

来源：

MOLECULAR CELL | 2014年 / 56卷 / 04期

基金：

俄罗斯科学基金会;

关键词：

ESCHERICHIA-COLI; PROTEIN-SYNTHESIS; TETRACYCLINE; ANTIBIOTICS; PACTAMYCIN; EDEINE; TARGET;

D O I：

10.1016/j.molcel.2014.09.020

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

We demonstrate that the antibiotic amicoumacin A (AMI) is a potent inhibitor of protein synthesis. Resistance mutations in helix 24 of the 16S rRNA mapped the AMI binding site to the small ribosomal subunit. The crystal structure of bacterial ribosome in complex with AMI solved at 2.4 angstrom resolution revealed that the antibiotic makes contacts with universally conserved nucleotides of 16S rRNA in the E site and the mRNA backbone. Simultaneous interactions of AMI with 16S rRNA and mRNA and the in vivo experimental evidence suggest that it may inhibit the progression of the ribosome along mRNA. Consistent with this proposal, binding of AMI interferes with translocation in vitro. The inhibitory action of AMI can be partly compensated by mutations in the translation elongation factor G.

引用

页码：531 / 540

页数：10

共 41 条

[1] Construction of Escherichia coli K-12 in-frame, single-gene knockout mutants:: the Keio collection [J].

Baba, Tomoya ;

Ara, Takeshi ;

Hasegawa, Miki ;

Takai, Yuki ;

Okumura, Yoshiko ;

Baba, Miki ;

Datsenko, Kirill A. ;

Tomita, Masaru ;

Wanner, Barry L. ;

Mori, Hirotada .

MOLECULAR SYSTEMS BIOLOGY, 2006, 2 (1) :2006.0008

[2] Nonoptimal Microbial Response to Antibiotics Underlies Suppressive Drug Interactions [J].

Bollenbach, Tobias ;

Quan, Selwyn ;

Chait, Remy ;

Kishony, Roy .

CELL, 2009, 139 (04) :707-718

[3] The structural basis for the action of the antibiotics tetracycline, pactamycin, and hygromycin B on the 30S ribosomal subunit [J].

Brodersen, DE ;

Clemons, WM ;

Carter, AP ;

Morgan-Warren, RJ ;

Wimberly, BT ;

Ramakrishnan, V .

CELL, 2000, 103 (07) :1143-1154

[4] PM-94128, a new isocoumarin antitumor agent produced by a marine bacterium [J].

Canedo, LM ;

Puentes, JLF ;

Baz, JP .

JOURNAL OF ANTIBIOTICS, 1997, 50 (02) :175-176

[5] Distinguishing On-Target versus Off-Target Activity in Early Antibacterial Drug Discovery Using a Macromolecular Synthesis Assay [J].

Cunningham, Mark L. ;

Kwan, Bryan P. ;

Nelson, Kirk J. ;

Bensen, Daniel C. ;

Shaw, Karen J. .

JOURNAL OF BIOMOLECULAR SCREENING, 2013, 18 (09) :1018-1026

[6] Modification of 16S ribosomal RNA by the KsgA methyltransferase restructures the 30S subunit to optimize ribosome function [J].

Demirci, Hasan ;

Murphy, Frank ;

Belardinelli, Riccardo ;

Kelley, Ann C. ;

Ramakrishnan, V. ;

Gregory, Steven T. ;

Dahlberg, Albert E. ;

Jogl, Gerwald .

RNA, 2010, 16 (12) :2319-2324

[7] Dissecting the ribosomal inhibition mechanisms of edeine and pactamycin: The universally conserved residues G693 and C795 regulate P-site RNA binding [J].

Dinos, G ;

Wilson, DN ;

Teraoka, Y ;

Szaflarski, W ;

Fucini, P ;

Kalpaxis, D ;

Nierhaus, KH .

MOLECULAR CELL, 2004, 13 (01) :113-124

[8] DEFINING THE STRUCTURAL REQUIREMENTS FOR A HELIX IN 23-S RIBOSOMAL-RNA THAT CONFERS ERYTHROMYCIN RESISTANCE [J].

DOUTHWAITE, S ;

POWERS, T ;

LEE, JY ;

NOLLER, HF .

JOURNAL OF MOLECULAR BIOLOGY, 1989, 209 (04) :655-665

[9] Tetracycline antibiotics and resistance mechanisms [J].

Fabian Nguyen ;

Starosta, Agata L. ;

Arenz, Stefan ;

Sohmen, Daniel ;

Doenhoefer, Alexandra ;

Wilson, Daniel N. .

BIOLOGICAL CHEMISTRY, 2014, 395 (05) :559-575

[10] Structure-based drug design meets the ribosome [J].

Franceschi, F ;

Duffy, EM .

BIOCHEMICAL PHARMACOLOGY, 2006, 71 (07) :1016-1025

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