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206 a.a.
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205 a.a.
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150 a.a.
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117 a.a.
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218 a.a.
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51 a.a.
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* Residue conservation analysis
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Obsolete entry |
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PDB id:
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| Name: |
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Ribosome
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Title:
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Crystal structure of the bacterial ribosome from escherichia coli in complex with ribosome recycling factor (rrf). This file contains the 30s subunit of the first 70s ribosome. The entire crystal structure contains two 70s ribosomes and is described in remark 400.
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Structure:
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16s rrna. Chain: a. 30s ribosomal protein s3. Chain: c. 30s ribosomal protein s4. Chain: d. 30s ribosomal protein s5. Chain: e. 30s ribosomal protein s6.
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Source:
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Escherichia coli. Organism_taxid: 562. Strain: mre600. Strain: mre600
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Resolution:
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3.30Å
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R-factor:
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0.275
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R-free:
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0.304
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Authors:
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M.A.Borovinskaya,R.D.Pai,W.Zhang,B.-S.Schuwirth,J.M.Holton, G.Hirokawa,H.Kaji,A.Kaji,J.H.D.Cate
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Key ref:
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M.A.Borovinskaya
et al.
(2007).
Structural basis for aminoglycoside inhibition of bacterial ribosome recycling.
Nat Struct Biol,
14,
727-732.
PubMed id:
DOI:
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Date:
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16-Jun-07
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Release date:
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25-Sep-07
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PROCHECK
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Headers
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References
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P0A7V3
(RS3_ECOLI) -
30S ribosomal protein S3 from Escherichia coli (strain K12)
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Seq: Struc:
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233 a.a.
206 a.a.
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P0A7V8
(RS4_ECOLI) -
30S ribosomal protein S4 from Escherichia coli (strain K12)
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Seq: Struc:
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206 a.a.
205 a.a.
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P0A7W1
(RS5_ECOLI) -
30S ribosomal protein S5 from Escherichia coli (strain K12)
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Seq: Struc:
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167 a.a.
150 a.a.
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P02358
(RS6_ECOLI) -
30S ribosomal protein S6 from Escherichia coli (strain K12)
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Seq: Struc:
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135 a.a.
100 a.a.
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P02359
(RS7_ECOLI) -
30S ribosomal protein S7 from Escherichia coli (strain K12)
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Seq: Struc:
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179 a.a.
150 a.a.
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P0A7W7
(RS8_ECOLI) -
30S ribosomal protein S8 from Escherichia coli (strain K12)
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Seq: Struc:
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130 a.a.
129 a.a.
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P0A7X3
(RS9_ECOLI) -
30S ribosomal protein S9 from Escherichia coli (strain K12)
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Seq: Struc:
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130 a.a.
127 a.a.
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P0A7R5
(RS10_ECOLI) -
30S ribosomal protein S10 from Escherichia coli (strain K12)
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Seq: Struc:
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103 a.a.
98 a.a.
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P0A7R9
(RS11_ECOLI) -
30S ribosomal protein S11 from Escherichia coli (strain K12)
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Seq: Struc:
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129 a.a.
117 a.a.
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P0A7S3
(RS12_ECOLI) -
30S ribosomal protein S12 from Escherichia coli (strain K12)
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Seq: Struc:
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124 a.a.
123 a.a.
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P0A7S9
(RS13_ECOLI) -
30S ribosomal protein S13 from Escherichia coli (strain K12)
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Seq: Struc:
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118 a.a.
114 a.a.
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P0AG59
(RS14_ECOLI) -
30S ribosomal protein S14 from Escherichia coli (strain K12)
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Seq: Struc:
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101 a.a.
96 a.a.
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P0ADZ4
(RS15_ECOLI) -
30S ribosomal protein S15 from Escherichia coli (strain K12)
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Seq: Struc:
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89 a.a.
88 a.a.
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P0A7T3
(RS16_ECOLI) -
30S ribosomal protein S16 from Escherichia coli (strain K12)
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Seq: Struc:
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82 a.a.
82 a.a.
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P0AG63
(RS17_ECOLI) -
30S ribosomal protein S17 from Escherichia coli (strain K12)
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|
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Seq: Struc:
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84 a.a.
80 a.a.
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P0A7T7
(RS18_ECOLI) -
30S ribosomal protein S18 from Escherichia coli (strain K12)
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Seq: Struc:
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75 a.a.
55 a.a.
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P0A7U3
(RS19_ECOLI) -
30S ribosomal protein S19 from Escherichia coli (strain K12)
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|
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Seq: Struc:
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92 a.a.
79 a.a.
|
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P0A7U7
(RS20_ECOLI) -
30S ribosomal protein S20 from Escherichia coli (strain K12)
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|
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Seq: Struc:
|
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87 a.a.
85 a.a.
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DOI no:
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Nat Struct Biol
14:727-732
(2007)
|
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PubMed id:
|
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| |
|
Structural basis for aminoglycoside inhibition of bacterial ribosome recycling.
|
|
M.A.Borovinskaya,
R.D.Pai,
W.Zhang,
B.S.Schuwirth,
J.M.Holton,
G.Hirokawa,
H.Kaji,
A.Kaji,
J.H.Cate.
|
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|
| |
ABSTRACT
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| |
|
Aminoglycosides are widely used antibiotics that cause messenger RNA decoding
errors, block mRNA and transfer RNA translocation, and inhibit ribosome
recycling. Ribosome recycling follows the termination of protein synthesis and
is aided by ribosome recycling factor (RRF) in bacteria. The molecular mechanism
by which aminoglycosides inhibit ribosome recycling is unknown. Here we show in
X-ray crystal structures of the Escherichia coli 70S ribosome that RRF binding
causes RNA helix H69 of the large ribosomal subunit, which is crucial for
subunit association, to swing away from the subunit interface. Aminoglycosides
bind to H69 and completely restore the contacts between ribosomal subunits that
are disrupted by RRF. These results provide a structural explanation for
aminoglycoside inhibition of ribosome recycling.
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| |
Selected figure(s)
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| |
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|
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Figure 1.
(a) Chemical structures of neomycin, paromomycin and
gentamicin. (b) Global view of the ribosome and the two binding
sites for aminoglycosides. Gold and green, aminoglycosides bound
to the 30S and 50S subunits, respectively; light blue, 16S rRNA;
gray, 23S rRNA; purple, 5S rRNA; dark blue and magenta, proteins
of small and large subunits, respectively; CP, central
protuberance. (c) Close-up view of the two binding sites in h44
and H69, shown with neomycin as an example. Neomycin molecules
bound to h44 and H69 are in gold and green, respectively. Green,
orange and blue shadows outline positions that would be occupied
by mRNA, A-site tRNA and P-site tRNA, respectively. The mRNA and
tRNAs are above the plane of the image. Inset shows direction of
view.
|
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Figure 3.
(a) F[o] – F[o] difference electron density map, truncated
at 6-Å resolution, comparing 70S ribosome crystals in
complex with RRF to ribosomes in complex with neomycin. In the
absence of RRF, the overall position of H69 at the interface in
apo–70S ribosomes is essentially identical to that in
neomycin-bound ribosomes (Supplementary Methods). Only domain I
of RRF is visible; domain II is located to the right of the view
shown. Blue, positive difference density; red, negative
difference density; arrow, direction of the conformational
change in H69 upon RRF binding. (b) F[o] – F[o] difference
electron density as in a, but at 3.5-Å resolution. Insets
in a and b show angles of view.
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| |
The above figures are
reprinted
by permission from Macmillan Publishers Ltd:
Nat Struct Biol
(2007,
14,
727-732)
copyright 2007.
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| |
Figures were
selected
by an automated process.
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Literature references that cite this PDB file's key reference
|
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| |
PubMed id
|
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Reference
|
 |
|
|
|
 |
L.Wang,
A.Pulk,
M.R.Wasserman,
M.B.Feldman,
R.B.Altman,
J.H.Doudna Cate,
and
S.C.Blanchard
(2012).
Allosteric control of the ribosome by small-molecule antibiotics.
|
| |
Nat Struct Mol Biol,
19,
957-963.
|
 |
|
PDB codes:
|
 |
|
|
|
|
|
 |
Y.Zhang,
and
M.Inouye
(2011).
RatA (YfjG), an Escherichia coli toxin, inhibits 70S ribosome association to block translation initiation.
|
| |
Mol Microbiol,
79,
1418-1429.
|
 |
|
|
|
|
 |
A.E.Scheunemann,
W.D.Graham,
F.A.Vendeix,
and
P.F.Agris
(2010).
Binding of aminoglycoside antibiotics to helix 69 of 23S rRNA.
|
| |
Nucleic Acids Res,
38,
3094-3105.
|
 |
|
|
|
|
 |
D.B.Johnson,
and
L.Wang
(2010).
Imprints of the genetic code in the ribosome.
|
| |
Proc Natl Acad Sci U S A,
107,
8298-8303.
|
 |
|
|
|
|
 |
D.E.Burakovsky,
P.V.Sergiev,
M.A.Steblyanko,
A.V.Kubarenko,
A.L.Konevega,
A.A.Bogdanov,
M.V.Rodnina,
and
O.A.Dontsova
(2010).
Mutations at the accommodation gate of the ribosome impair RF2-dependent translation termination.
|
| |
RNA,
16,
1848-1853.
|
 |
|
|
|
|
 |
E.B.Kramer,
H.Vallabhaneni,
L.M.Mayer,
and
P.J.Farabaugh
(2010).
A comprehensive analysis of translational missense errors in the yeast Saccharomyces cerevisiae.
|
| |
RNA,
16,
1797-1808.
|
 |
|
|
|
|
 |
F.Babić,
V.Venturi,
and
G.Maravić-Vlahovicek
(2010).
Tobramycin at subinhibitory concentration inhibits the RhlI/R quorum sensing system in a Pseudomonas aeruginosa environmental isolate.
|
| |
BMC Infect Dis,
10,
148.
|
 |
|
|
|
|
 |
H.David-Eden,
A.S.Mankin,
and
Y.Mandel-Gutfreund
(2010).
Structural signatures of antibiotic binding sites on the ribosome.
|
| |
Nucleic Acids Res,
38,
5982-5994.
|
 |
|
|
|
|
 |
M.B.Feldman,
D.S.Terry,
R.B.Altman,
and
S.C.Blanchard
(2010).
Aminoglycoside activity observed on single pre-translocation ribosome complexes.
|
| |
Nat Chem Biol,
6,
54-62.
|
 |
|
|
|
|
 |
P.B.Tsitovich,
A.Pushechnikov,
J.M.French,
and
M.D.Disney
(2010).
A chemoenzymatic route to diversify aminoglycosides enables a microarray-based method to probe acetyltransferase activity.
|
| |
Chembiochem,
11,
1656-1660.
|
 |
|
|
|
|
 |
R.E.Stanley,
G.Blaha,
R.L.Grodzicki,
M.D.Strickler,
and
T.A.Steitz
(2010).
The structures of the anti-tuberculosis antibiotics viomycin and capreomycin bound to the 70S ribosome.
|
| |
Nat Struct Mol Biol,
17,
289-293.
|
 |
|
PDB codes:
|
 |
|
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|
 |
T.Tran,
and
M.D.Disney
(2010).
Two-dimensional combinatorial screening of a bacterial rRNA A-site-like motif library: defining privileged asymmetric internal loops that bind aminoglycosides.
|
| |
Biochemistry,
49,
1833-1842.
|
 |
|
|
|
|
 |
A.Baudin-Baillieu,
C.Fabret,
X.H.Liang,
D.Piekna-Przybylska,
M.J.Fournier,
and
J.P.Rousset
(2009).
Nucleotide modifications in three functionally important regions of the Saccharomyces cerevisiae ribosome affect translation accuracy.
|
| |
Nucleic Acids Res,
37,
7665-7677.
|
 |
|
|
|
|
 |
A.Savelsbergh,
M.V.Rodnina,
and
W.Wintermeyer
(2009).
Distinct functions of elongation factor G in ribosome recycling and translocation.
|
| |
RNA,
15,
772-780.
|
 |
|
|
|
|
 |
A.Yonath
(2009).
Large facilities and the evolving ribosome, the cellular machine for genetic-code translation.
|
| |
J R Soc Interface,
6,
S575-S585.
|
 |
|
|
|
|
 |
B.A.Maguire
(2009).
Inhibition of bacterial ribosome assembly: a suitable drug target?
|
| |
Microbiol Mol Biol Rev,
73,
22-35.
|
 |
|
|
|
|
 |
D.J.Paul,
S.J.Seedhouse,
and
M.D.Disney
(2009).
Two-dimensional combinatorial screening and the RNA Privileged Space Predictor program efficiently identify aminoglycoside-RNA hairpin loop interactions.
|
| |
Nucleic Acids Res,
37,
5894-5907.
|
 |
|
|
|
|
 |
D.N.Wilson
(2009).
The A-Z of bacterial translation inhibitors.
|
| |
Crit Rev Biochem Mol Biol,
44,
393-433.
|
 |
|
|
|
|
 |
L.E.Holberger,
and
C.S.Hayes
(2009).
Ribosomal protein S12 and aminoglycoside antibiotics modulate A-site mRNA cleavage and transfer-messenger RNA activity in Escherichia coli.
|
| |
J Biol Chem,
284,
32188-32200.
|
 |
|
|
|
|
 |
M.A.Zundel,
G.N.Basturea,
and
M.P.Deutscher
(2009).
Initiation of ribosome degradation during starvation in Escherichia coli.
|
| |
RNA,
15,
977-983.
|
 |
|
|
|
|
 |
M.O'Connor
(2009).
Helix 69 in 23S rRNA modulates decoding by wild type and suppressor tRNAs.
|
| |
Mol Genet Genomics,
282,
371-380.
|
 |
|
|
|
|
 |
M.Savic,
J.Lovric,
T.I.Tomic,
B.Vasiljevic,
and
G.L.Conn
(2009).
Determination of the target nucleosides for members of two families of 16S rRNA methyltransferases that confer resistance to partially overlapping groups of aminoglycoside antibiotics.
|
| |
Nucleic Acids Res,
37,
5420-5431.
|
 |
|
|
|
|
 |
S.H.Sternberg,
J.Fei,
N.Prywes,
K.A.McGrath,
and
R.L.Gonzalez
(2009).
Translation factors direct intrinsic ribosome dynamics during translation termination and ribosome recycling.
|
| |
Nat Struct Mol Biol,
16,
861-868.
|
 |
|
|
|
|
 |
T.M.Schmeing,
and
V.Ramakrishnan
(2009).
What recent ribosome structures have revealed about the mechanism of translation.
|
| |
Nature,
461,
1234-1242.
|
 |
|
|
|
|
 |
X.G.Zhang,
P.W.Mason,
E.J.Dubovi,
X.Xu,
N.Bourne,
R.W.Renshaw,
T.M.Block,
and
A.V.Birk
(2009).
Antiviral activity of geneticin against dengue virus.
|
| |
Antiviral Res,
83,
21-27.
|
 |
|
|
|
|
 |
A.Korostelev,
H.Asahara,
L.Lancaster,
M.Laurberg,
A.Hirschi,
J.Zhu,
S.Trakhanov,
W.G.Scott,
and
H.F.Noller
(2008).
Crystal structure of a translation termination complex formed with release factor RF2.
|
| |
Proc Natl Acad Sci U S A,
105,
19684-19689.
|
 |
|
PDB codes:
|
 |
|
|
|
|
|
 |
C.Foster,
and
W.S.Champney
(2008).
Characterization of a 30S ribosomal subunit assembly intermediate found in Escherichia coli cells growing with neomycin or paromomycin.
|
| |
Arch Microbiol,
189,
441-449.
|
 |
|
|
|
|
 |
G.Hirokawa,
N.Iwakura,
A.Kaji,
and
H.Kaji
(2008).
The role of GTP in transient splitting of 70S ribosomes by RRF (ribosome recycling factor) and EF-G (elongation factor G).
|
| |
Nucleic Acids Res,
36,
6676-6687.
|
 |
|
|
|
|
 |
J.P.Desaulniers,
Y.C.Chang,
R.Aduri,
S.C.Abeysirigunawardena,
J.SantaLucia,
and
C.S.Chow
(2008).
Pseudouridines in rRNA helix 69 play a role in loop stacking interactions.
|
| |
Org Biomol Chem,
6,
3892-3895.
|
 |
|
|
|
|
 |
M.A.Borovinskaya,
S.Shoji,
K.Fredrick,
and
J.H.Cate
(2008).
Structural basis for hygromycin B inhibition of protein biosynthesis.
|
| |
RNA,
14,
1590-1599.
|
 |
|
PDB codes:
|
 |
|
|
|
|
|
 |
N.M.Llewellyn,
and
J.B.Spencer
(2008).
Chemoenzymatic acylation of aminoglycoside antibiotics.
|
| |
Chem Commun (Camb),
(),
3786-3788.
|
 |
|
|
|
|
 |
R.D.Pai,
W.Zhang,
B.S.Schuwirth,
G.Hirokawa,
H.Kaji,
A.Kaji,
and
J.H.Cate
(2008).
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PDB code:
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The most recent references are shown first.
Citation data come partly from CiteXplore and partly
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Where a reference describes a PDB structure, the PDB
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}
}
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