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PDBsum entry 2a6h
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Contents |
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229 a.a.
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1119 a.a.
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1381 a.a.
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95 a.a.
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345 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 of transcription inhibition by antibiotic streptolydigin.
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Authors
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D.Temiakov,
N.Zenkin,
M.N.Vassylyeva,
A.Perederina,
T.H.Tahirov,
E.Kashkina,
M.Savkina,
S.Zorov,
V.Nikiforov,
N.Igarashi,
N.Matsugaki,
S.Wakatsuki,
K.Severinov,
D.G.Vassylyev.
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Ref.
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Mol Cell, 2005,
19,
655-666.
[DOI no: ]
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PubMed id
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Abstract
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Streptolydigin (Stl) is a potent inhibitor of bacterial RNA polymerases (RNAPs).
The 2.4 A resolution structure of the Thermus thermophilus RNAP-Stl complex
showed that, in full agreement with the available genetic data, the inhibitor
binding site is located 20 A away from the RNAP active site and encompasses the
bridge helix and the trigger loop, two elements that are considered to be
crucial for RNAP catalytic center function. Structure-based biochemical
experiments revealed additional determinants of Stl binding and demonstrated
that Stl does not affect NTP substrate binding, DNA translocation, and
phosphodiester bond formation. The RNAP-Stl complex structure, its comparison
with the closely related substrate bound eukaryotic transcription elongation
complexes, and biochemical analysis suggest an inhibitory mechanism in which Stl
stabilizes catalytically inactive (preinsertion) substrate bound transcription
intermediate, thereby blocking structural isomerization of RNAP to an active
configuration. The results provide a basis for a design of new antibiotics
utilizing the Stl-like mechanism.
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Figure 1.
Figure 1. The RNAP-Stl Complex Structure
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Figure 5.
Figure 5. Substrate Loading in the IS and Plausible
Mechanism of Stl Action
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The above figures are
reprinted
by permission from Cell Press:
Mol Cell
(2005,
19,
655-666)
copyright 2005.
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