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PDBsum entry 1jzz
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Contents |
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197 a.a.*
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130 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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Structural basis for the interaction of antibiotics with the peptidyl transferase centre in eubacteria.
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Authors
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F.Schlünzen,
R.Zarivach,
J.Harms,
A.Bashan,
A.Tocilj,
R.Albrecht,
A.Yonath,
F.Franceschi.
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Ref.
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Nature, 2001,
413,
814-821.
[DOI no: ]
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PubMed id
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Abstract
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Ribosomes, the site of protein synthesis, are a major target for natural and
synthetic antibiotics. Detailed knowledge of antibiotic binding sites is central
to understanding the mechanisms of drug action. Conversely, drugs are excellent
tools for studying the ribosome function. To elucidate the structural basis of
ribosome-antibiotic interactions, we determined the high-resolution X-ray
structures of the 50S ribosomal subunit of the eubacterium Deinococcus
radiodurans, complexed with the clinically relevant antibiotics chloramphenicol,
clindamycin and the three macrolides erythromycin, clarithromycin and
roxithromycin. We found that antibiotic binding sites are composed exclusively
of segments of 23S ribosomal RNA at the peptidyl transferase cavity and do not
involve any interaction of the drugs with ribosomal proteins. Here we report the
details of antibiotic interactions with the components of their binding sites.
Our results also show the importance of putative Mg+2 ions for the binding of
some drugs. This structural analysis should facilitate rational drug design.
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Figure 1.
Figure 1: Interaction of chloramphenicol with the peptidyl
transferase cavity. a, Chemical structure diagram of
chloramphenicol showing the interactions (arrows) of its
reactive groups with the nucleotides of the peptidyl transferase
cavity. Arrows between two chemical moieties indicate that the
two groups are less than 4.4 Å apart. b, Secondary structure of
the peptidyl transferase ring of D. radiodurans showing the
nucleotides involved in the interaction with chloramphenicol
(coloured nucleotides). The colours in the secondary structure
diagram match those of the chemical diagram. c, Stereo view
showing the nucleotides interacting with chloramphenicol at the
peptidyl transferase cavity of D. radiodurans. The difference
electron density map (2F[o] - F[c]) is contoured at 1.2  .
The antibiotic is shown in green. Nucleotide numbering is
according to the E. coli sequence. Putative Mg ions (Mg-C1,
Mg-C2) are indicated.
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Figure 4.
Figure 4: Relative position of chloramphenicol, clindamycin and
macrolides with respect to CC-puromycin and the
3'-cytosine-adenine (CA) end of P-site and A-site tRNAs. The
location of CC-puromycin was obtained by docking the position
reported by ref. 2 into the peptidyl transferase centre of D.
radiodurans. The location of the 3'-CA end of P- and A-site
tRNAs was obtained by docking the position reported by ref. 42
into the peptidyl transferase centre of D. radiodurans. Light
blue, 3'-CA end of A-site tRNA; light yellow, 3'-CA end of
P-site tRNA; grey, puromycin; gold, chloramphenicol; green,
clindamycin; cyan, macrolides (erythromycin). Oxygen atoms are
shown in red and nitrogen atoms in dark blue. CHCl[2] indicates
the location of the dichloromethyl moiety of chloramphenicol.
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The above figures are
reprinted
by permission from Macmillan Publishers Ltd:
Nature
(2001,
413,
814-821)
copyright 2001.
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Headers
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