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PDBsum entry 3d1f
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Transferase, transcription
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PDB id
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3d1f
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References listed in PDB file
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Key reference
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Title
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Structure of a small-Molecule inhibitor of a DNA polymerase sliding clamp.
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Authors
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R.E.Georgescu,
O.Yurieva,
S.S.Kim,
J.Kuriyan,
X.P.Kong,
M.O'Donnell.
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Ref.
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Proc Natl Acad Sci U S A, 2008,
105,
11116-11121.
[DOI no: ]
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PubMed id
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Abstract
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DNA polymerases attach to the DNA sliding clamp through a common overlapping
binding site. We identify a small-molecule compound that binds the
protein-binding site in the Escherichia coli beta-clamp and differentially
affects the activity of DNA polymerases II, III, and IV. To understand the
molecular basis of this discrimination, the cocrystal structure of the chemical
inhibitor is solved in complex with beta and is compared with the structures of
Pol II, Pol III, and Pol IV peptides bound to beta. The analysis reveals that
the small molecule localizes in a region of the clamp to which the DNA
polymerases attach in different ways. The results suggest that the small
molecule may be useful in the future to probe polymerase function with beta, and
that the beta-clamp may represent an antibiotic target.
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Figure 3.
Structure of a small-molecule inhibitor bound to the
β-clamp. (A) The RU7 compound. (B) Distances between RU7 and
the β-clamp. Side-chain movements upon binding RU7 are
indicated. Yellow and white are residues of β in the absence or
presence of RU7, respectively. Distances between RU7 and protein
residues are marked in black; the distances 3.73, 3.41, and 3.03
Å are marked a, b, and c, respectively.
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Figure 5.
Superposition of Pol II, III, and IV peptides and RU7
compound bound to β. (A) Superposition of the Pol III peptide
(green), Pol II peptide (blue), and Pol IV peptide (purple; PDB
ID code 1OK7) (10). (B) Superposition of Pol III peptide (green)
and the RU7 compound (orange). The surface of the β-clamp is
colored white, and the protein-binding pocket of β is colored
according to sequence conservation of an alignment of 42
bacterial subunits; the color scale proceeds from red (90%
conservation) to yellow (50% conservation). Circled regions in
the peptide-binding pocket indicate subsites 1 and 2. Figures
were prepared by using Pymol (27).
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