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PDBsum entry 3bbc
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References listed in PDB file
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Key reference
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Title
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Nm23-H2 may play an indirect role in transcriptional activation of c-Myc gene expression but does not cleave the nuclease hypersensitive element III(1).
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Authors
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T.S.Dexheimer,
S.S.Carey,
S.Zuohe,
V.M.Gokhale,
X.Hu,
L.B.Murata,
E.M.Maes,
A.Weichsel,
D.Sun,
E.J.Meuillet,
W.R.Montfort,
L.H.Hurley.
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Ref.
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Mol Cancer Ther, 2009,
8,
1363-1377.
[DOI no: ]
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PubMed id
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Abstract
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The formation of G-quadruplex structures within the nuclease hypersensitive
element (NHE) III(1) region of the c-myc promoter and the ability of these
structures to repress c-myc transcription have been well established. However,
just how these extremely stable DNA secondary structures are transformed to
activate c-myc transcription is still unknown. NM23-H2/nucleoside diphosphate
kinase B has been recognized as an activator of c-myc transcription via
interactions with the NHE III(1) region of the c-myc gene promoter. Through the
use of RNA interference, we confirmed the transcriptional regulatory role of
NM23-H2. In addition, we find that further purification of NM23-H2 results in
loss of the previously identified DNA strand cleavage activity, but retention of
its DNA binding activity. NM23-H2 binds to both single-stranded guanine- and
cytosine-rich strands of the c-myc NHE III(1) and, to a lesser extent, to a
random single-stranded DNA template. However, it does not bind to or cleave the
NHE III(1) in duplex form. Significantly, potassium ions and compounds that
stabilize the G-quadruplex and i-motif structures have an inhibitory effect on
NM23-H2 DNA-binding activity. Mutation of Arg(88) to Ala(88) (R88A) reduced both
DNA and nucleotide binding but had minimal effect on the NM23-H2 crystal
structure. On the basis of these data and molecular modeling studies, we have
proposed a stepwise trapping-out of the NHE III(1) region in a single-stranded
form, thus allowing single-stranded transcription factors to bind and activate
c-myc transcription. Furthermore, this model provides a rationale for how the
stabilization of the G-quadruplex or i-motif structures formed within the c-myc
gene promoter region can inhibit NM23-H2 from activating c-myc gene expression.
[Mol Cancer Ther 2009;8(5):1363-77].
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Secondary reference #1
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Title
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X-Ray structure of human nucleoside diphosphate kinase b complexed with gdp at 2 a resolution.
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Authors
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S.Moréra,
M.L.Lacombe,
Y.Xu,
G.Lebras,
J.Janin.
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Ref.
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Structure, 1995,
3,
1307-1314.
[DOI no: ]
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PubMed id
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Figure 1.
Figure 1. . The NDP kinase B hexamer. (a) A view along the
threefold axis. (b) View along a twofold axis in an orthogonal
direction. α helices are in red and β strands are in blue.
Helices α[1] and α[3] and the Kpn loops (yellow) form the core
of the hexamer. The Kpn loops are at the poles of the molecule,
near the threefold axis; helices α[A], α[2] and α[4], and
the C-terminal extended segment are on the equator. Blue Van
der Waals atoms represent bound GDP molecules. Figure 1. .
The NDP kinase B hexamer. (a) A view along the threefold axis.
(b) View along a twofold axis in an orthogonal direction. α
helices are in red and β strands are in blue. Helices α[1] and
α[3] and the Kpn loops (yellow) form the core of the hexamer.
The Kpn loops are at the poles of the molecule, near the
threefold axis; helices α[A], α[2] and α[4], and the
C-terminal extended segment are on the equator. Blue Van der
Waals atoms represent bound GDP molecules. (The figure was drawn
with MOLSCRIPT [[4]38] with Raster3D [[5]39] rendering.)
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Figure 3.
Figure 3. . Electron density for bound GDP. The F[o]–F[c] map
is contoured at 2σ. Figure 3. . Electron density for bound
GDP. The F[o]–F[c] map is contoured at 2σ. (The figure was
drawn with TURBO, Drs A Roussel and C Cambillau, Marseille,
France.)
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The above figures are
reproduced from the cited reference
with permission from Cell Press
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