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PDBsum entry 4tpc
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Contents |
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218 a.a.
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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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151 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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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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Synergy of streptogramin antibiotics occurs independently of their effects on translation.
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Authors
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J.Noeske,
J.Huang,
N.B.Olivier,
R.A.Giacobbe,
M.Zambrowski,
J.H.Cate.
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Ref.
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Antimicrob Agents Chemother, 2014,
58,
5269-5279.
[DOI no: ]
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PubMed id
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Abstract
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Streptogramin antibiotics are divided into types A and B, which in combination
can act synergistically. We compared the molecular interactions of the
streptogramin combinations Synercid (type A, dalfopristin; type B, quinupristin)
and NXL 103 (type A, flopristin; type B, linopristin) with the Escherichia coli
70S ribosome by X-ray crystallography. We further analyzed the activity of the
streptogramin components individually and in combination. The streptogramin A
and B components in Synercid and NXL 103 exhibit synergistic antimicrobial
activity against certain pathogenic bacteria. However, in transcription-coupled
translation assays, only combinations that include dalfopristin, the
streptogramin A component of Synercid, show synergy. Notably, the
diethylaminoethylsulfonyl group in dalfopristin reduces its activity but is the
basis for synergy in transcription-coupled translation assays before its rapid
hydrolysis from the depsipeptide core. Replacement of the
diethylaminoethylsulfonyl group in dalfopristin by a nonhydrolyzable group may
therefore be beneficial for synergy. The absence of general streptogramin
synergy in transcription-coupled translation assays suggests that the
synergistic antimicrobial activity of streptogramins can occur independently of
the effects of streptogramin on translation.
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