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PDBsum entry 2qb9
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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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100 a.a.
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150 a.a.
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129 a.a.
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127 a.a.
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98 a.a.
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117 a.a.
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123 a.a.
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114 a.a.
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96 a.a.
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88 a.a.
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82 a.a.
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80 a.a.
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55 a.a.
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79 a.a.
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85 a.a.
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218 a.a.
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51 a.a.
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References listed in PDB file
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Key reference
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Title
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Structural basis for aminoglycoside inhibition of bacterial ribosome recycling.
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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.Cate.
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Ref.
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Nat Struct Biol, 2007,
14,
727-732.
[DOI no: ]
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PubMed id
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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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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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