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PDBsum entry 3cf5
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Ribosome/antibiotic
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PDB id
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3cf5
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Contents |
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53 a.a.*
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46 a.a.*
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63 a.a.*
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37 a.a.
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19 a.a.
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240 a.a.
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205 a.a.
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197 a.a.
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177 a.a.
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171 a.a.
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144 a.a.
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142 a.a.
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134 a.a.
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141 a.a.
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136 a.a.
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113 a.a.
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104 a.a.
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108 a.a.
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117 a.a.
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94 a.a.
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127 a.a.
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93 a.a.
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110 a.a.
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175 a.a.
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84 a.a.
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72 a.a.
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66 a.a.
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55 a.a.
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58 a.a.
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* C-alpha coords only
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References listed in PDB file
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Key reference
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Title
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Translational regulation via l11: molecular switches on the ribosome turned on and off by thiostrepton and micrococcin.
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Authors
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J.M.Harms,
D.N.Wilson,
F.Schluenzen,
S.R.Connell,
T.Stachelhaus,
Z.Zaborowska,
C.M.Spahn,
P.Fucini.
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Ref.
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Mol Cell, 2008,
30,
26-38.
[DOI no: ]
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PubMed id
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Abstract
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The thiopeptide class of antibiotics targets the GTPase-associated center (GAC)
of the ribosome to inhibit translation factor function. Using X-ray
crystallography, we have determined the binding sites of thiostrepton (Thio),
nosiheptide (Nosi), and micrococcin (Micro), on the Deinococcus radiodurans
large ribosomal subunit. The thiopeptides, by binding within a cleft located
between the ribosomal protein L11 and helices 43 and 44 of the 23S rRNA, overlap
with the position of domain V of EF-G, thus explaining how this class of drugs
perturbs translation factor binding to the ribosome. The presence of Micro leads
to additional density for the C-terminal domain (CTD) of L7, adjacent to and
interacting with L11. The results suggest that L11 acts as a molecular switch to
control L7 binding and plays a pivotal role in positioning one L7-CTD monomer on
the G' subdomain of EF-G to regulate EF-G turnover during protein synthesis.
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Figure 2.
Figure 2. Binding Position of Thio and Nosi on the 50S
Subunit
(A) Overview of thiopeptide binding site on the D.
radiodurans 50S subunit. Interface view of the 50S subunit (rRNA
and r-proteins colored light and dark blue, respectively) with
the thiopeptide binding site boxed. Enlargement of boxed region
reveals that the thiopeptides Thio (cyan) and Nosi (green) bind
within a cleft between the N-terminal domain (NTD) of r-protein
L11 (yellow) and the 23S rRNA H43 and H44 (orange).
(B and
C) 2mF[o] − DF[c] σ[A]-weighted difference electron density
maps (meshed) contoured to 2σ with (B) Thio, (C) Nosi, L11-NTD,
and H44 colored as in (A).
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Figure 6.
Figure 6. Schematic for EF-G and Thiopeptide Action during
Translation
(A–D) Model for events leading to EF-G
accommodation on the ribosome and Pi release as described in the
text. Effect of (E) Thio (purple) and (F) Micro (brown) are also
shown schematically. Individual domains of EF-G (orange) are
labeled with II-V and G/G′, and the stalk base (SB) components
are indicated with L11 (green) divided into with N- and
C-terminal domains (NTD, CTD) and rRNA helices H43 and H44
(blue). The C-terminal domain of L7 (L7-CTD) is shown in red.
Note that for simplicity, the switching mechanism has been
divided into two distinct steps; however, it is unclear as to
whether they are sequential, as shown here, or occur
simultaneously.
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The above figures are
reprinted
by permission from Cell Press:
Mol Cell
(2008,
30,
26-38)
copyright 2008.
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