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PDBsum entry 4oir
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Transcription, transferase/antibiotic
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PDB id
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4oir
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Contents |
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231 a.a.
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1112 a.a.
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1485 a.a.
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94 a.a.
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346 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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Ge23077 binds to the RNA polymerase 'I' And 'I+1' Sites and prevents the binding of initiating nucleotides.
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Authors
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Y.Zhang,
D.Degen,
M.X.Ho,
E.Sineva,
K.Y.Ebright,
Y.W.Ebright,
V.Mekler,
H.Vahedian-Movahed,
Y.Feng,
R.Yin,
S.Tuske,
H.Irschik,
R.Jansen,
S.Maffioli,
S.Donadio,
E.Arnold,
R.H.Ebright.
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Ref.
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Elife, 2014,
3,
e02450.
[DOI no: ]
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PubMed id
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Abstract
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Using a combination of genetic, biochemical, and structural approaches, we show
that the cyclic-peptide antibiotic GE23077 (GE) binds directly to the bacterial
RNA polymerase (RNAP) active-center 'i' and 'i+1' nucleotide binding sites,
preventing the binding of initiating nucleotides, and thereby preventing
transcription initiation. The target-based resistance spectrum for GE is
unusually small, reflecting the fact that the GE binding site on RNAP includes
residues of the RNAP active center that cannot be substituted without loss of
RNAP activity. The GE binding site on RNAP is different from the rifamycin
binding site. Accordingly, GE and rifamycins do not exhibit cross-resistance,
and GE and a rifamycin can bind simultaneously to RNAP. The GE binding site on
RNAP is immediately adjacent to the rifamycin binding site. Accordingly,
covalent linkage of GE to a rifamycin provides a bipartite inhibitor having very
high potency and very low susceptibility to target-based resistance. DOI:
http://dx.doi.org/10.7554/eLife.02450.001.
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