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PDBsum entry 1f9f
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Transcription
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PDB id
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1f9f
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Contents |
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76 a.a.
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77 a.a.
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76 a.a.
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82 a.a.
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* Residue conservation analysis
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References listed in PDB file
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Key reference
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Title
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The structural basis of DNA target discrimination by papillomavirus e2 proteins.
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Authors
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S.S.Kim,
J.K.Tam,
A.F.Wang,
R.S.Hegde.
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Ref.
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J Biol Chem, 2000,
275,
31245-31254.
[DOI no: ]
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PubMed id
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Abstract
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The papillomavirus E2 proteins regulate the transcription of all papillomavirus
genes and are necessary for viral DNA replication. Disruption of the E2 gene is
commonly associated with malignancy in cervical carcinoma, indicating that E2
has a role in regulating tumor progression. Although the E2 proteins from all
characterized papillomaviruses bind specifically to the same 12-base pair DNA
sequence, the cancer-associated human papillomavirus E2 proteins display a
unique ability to detect DNA flexibility and intrinsic curvature. To understand
the structural basis for this phenomenon, we have determined the crystal
structures of the human papillomavirus-18 E2 DNA-binding domain and its
complexes with high and low affinity binding sites. The E2 protein is a dimeric
beta-barrel and the E2-DNA interaction is accompanied by a large deformation of
the DNA as it conforms to the E2 surface. DNA conformation and E2-DNA contacts
are similar in both high and low affinity complexes. The differences in affinity
correlate with the flexibility of the DNA sequence. Preferences of E2 proteins
from different papillomavirus strains for flexible or prevent DNA targets
correlate with the distribution of positive charge on their DNA interaction
surfaces, suggesting a role for electrostatic forces in the recognition of DNA
deformability.
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Figure 3.
Fig. 3. Design of oligonucleotides used.
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Figure 6.
Fig. 6. a, comparison of the HPV-18 E2/D protein in the
free (green) and DNA-bound (gold) states. The left subunit is
superimposed. b, comparison of the complexes formed by HPV-18
E2/D (gold) and BPV-1 E2/D (blue) with E2BS(AATT). The left
subunit of each protein is superimposed. c, the intersubunit
interactions between side chains in the  [2]/ [3] loop and
the C-terminal region of the recognition helix in the BPV-1
E2/D-E2BS(AATT) complex. The backbone worm representing relevant
regions of the two subunits are shown in different colors.
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The above figures are
reprinted
by permission from the ASBMB:
J Biol Chem
(2000,
275,
31245-31254)
copyright 2000.
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