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PDBsum entry 3hdd
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Transcription/DNA
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PDB id
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3hdd
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Contents |
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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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Engrailed homeodomain-Dna complex at 2.2 a resolution: a detailed view of the interface and comparison with other engrailed structures.
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Authors
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E.Fraenkel,
M.A.Rould,
K.A.Chambers,
C.O.Pabo.
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Ref.
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J Mol Biol, 1998,
284,
351-361.
[DOI no: ]
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PubMed id
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Note In the PDB file this reference is
annotated as "TO BE PUBLISHED".
The citation details given above were identified by an automated
search of PubMed on title and author
names, giving a
perfect match.
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Abstract
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We report the 2.2 A resolution structure of the Drosophila engrailed homeodomain
bound to its optimal DNA site. The original 2.8 A resolution structure of this
complex provided the first detailed three-dimensional view of how homeodomains
recognize DNA, and has served as the basis for biochemical studies, structural
studies and molecular modeling. Our refined structure confirms the principal
conclusions of the original structure, but provides important new details about
the recognition interface. Biochemical and NMR studies of other homeodomains had
led to the notion that Gln50 was an especially important determinant of
specificity. However, our refined structure shows that this side-chain makes no
direct hydrogen bonds to the DNA. The structure does reveal an extensive network
of ordered water molecules which mediate contacts to several bases and
phosphates (including contacts from Gln50), and our model provides a basis for
detailed comparison with the structure of an engrailed Q50K altered-specificity
variant. Comparing our structure with the crystal structure of the free protein
confirms that the N and C termini of the homeodomain become ordered upon
DNA-binding. However, we also find that several key DNA contact residues in the
recognition helix have the same conformation in the free and bound protein, and
that several water molecules also are "preorganized" to contact the
DNA. Our structure helps provide a more complete basis for the detailed analysis
of homeodomain-DNA interactions.
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Figure 2.
Figure 2. A, Diagram showing major groove contacts made by
wild-type and Q50K engrailed [Tucker-Kellogg et al 1997]. The
DNA is represented as a cylindrical projection with phosphates
shown as circles; phosphates contacted by the protein are
shaded. Contacts from the protein backbone to the DNA are
indicated by an oval around the name of the residue. Water
molecules in the structure of wild-type engrailed that were also
observed in the structure of the free protein are enclosed in
boxes. Superimposing the free and bound proteins gives an rms
distance. of 0.55 Å for these six water molecules. Those
water molecules which surround Ala54 are shaded gray. B, Stereo
view of the protein-DNA interface in the wild-type engrailed-DNA
complex. DNA is shown in blue with the protein in red. Water
molecules are indicated by light blue spheres and hydrogen bonds
by broken lines.
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Figure 3.
Figure 3. Stereo view showing interactions of the
recognition helix in the major groove of engrailed. The backbone
of residues 47 to 54 from the recognition helix is shown in red,
and base-pairs 3 to 7 are shown in blue. Side-chains of Ile47,
Gln50, Asn51 and Ala54 are yellow, with water molecules shown in
light blue. Hydrogen bonds are indicated by golden spheres.
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The above figures are
reprinted
by permission from Elsevier:
J Mol Biol
(1998,
284,
351-361)
copyright 1998.
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