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PDBsum entry 1dg3
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Signaling protein
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PDB id
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1dg3
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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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Structure of human guanylate-Binding protein 1 representing a unique class of gtp-Binding proteins.
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Authors
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B.Prakash,
G.J.Praefcke,
L.Renault,
A.Wittinghofer,
C.Herrmann.
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Ref.
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Nature, 2000,
403,
567-571.
[DOI no: ]
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PubMed id
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Abstract
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Interferon-gamma is an immunomodulatory substance that induces the expression of
many genes to orchestrate a cellular response and establish the antiviral state
of the cell. Among the most abundant antiviral proteins induced by
interferon-gamma are guanylate-binding proteins such as GBP1 and GBP2. These are
large GTP-binding proteins of relative molecular mass 67,000 with a
high-turnover GTPase activity and an antiviral effect. Here we have determined
the crystal structure of full-length human GBP1 to 1.8 A resolution. The
amino-terminal 278 residues constitute a modified G domain with a number of
insertions compared to the canonical Ras structure, and the carboxy-terminal
part is an extended helical domain with unique features. From the structure and
biochemical experiments reported here, GBP1 appears to belong to the group of
large GTP-binding proteins that includes Mx and dynamin, the common property of
which is the ability to undergo oligomerization with a high
concentration-dependent GTPase activity.
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Figure 2.
Figure 2: Comparison of hGBP1 and Ras structures. a,
Superimposition of the LG domain of hGBP1 with the G domain of
Ras in complex with GDP(PDB accession no. 1Q21) as a stereo
view. N-terminal residues 1-36 of hGBP1 up to  1
have been omitted for clarity. The colour code is as in Fig. 1;
Ras is in cyan. b, Putative location of nucleotide-binding site
in hGBP1. The regions of hGBP1 potentially involved in binding
the guanine nucleotide are shown as obtained from a structural
superimposition of RasGDP (in cyan) with the corresponding
regions in hGBP1 (purple), highlighting functionally important
residues necessary for binding and conformational change as
balls or in ball-and-stick. Whereas Gly 60^ras overlays very
well with Gly 100^hGBP1, residues D119/D184 and T35/T75 do not.
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Figure 3.
Figure 3: Interaction of the C-terminal helix motif alpha- 12/13
with the helical and the LG domains. The electrostatic
surface potential shows that the highly charged regions of the
helical and LG domains are masked by an  12/13
motif, as indicated in the lower panel by showing 12/
13
in worm representation.
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The above figures are
reprinted
by permission from Macmillan Publishers Ltd:
Nature
(2000,
403,
567-571)
copyright 2000.
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Secondary reference #1
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Title
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Nucleotide-Binding characteristics of human guanylate-Binding protein 1 (hgbp1) and identification of the third gtp-Binding motif.
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Authors
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G.J.Praefcke,
M.Geyer,
M.Schwemmle,
H.Robert kalbitzer,
C.Herrmann.
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Ref.
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J Mol Biol, 1999,
292,
321-332.
[DOI no: ]
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PubMed id
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Figure 5.
Figure 5. (a) Fluorescence spectra (excited at 366 nm) of
1.0 µM mant-GDP only (1), and after subsequent addition of
10 µM hGBP1 (2), 10 mM NaF (3) and 70 µM AlCl[3](4).
(b) Corresponding experiment with mant-GMPPNP.
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Figure 7.
Figure 7. Titration of (a) mant-GMPPNP at 2.3 µM and
(b) of mant-XMPPNP at 0.5 µM with hGBP1 wild-type
(squares) and D184N (circles). The fluorescence was excited at
366 nm and detected at 435 nm.
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The above figures are
reproduced from the cited reference
with permission from Elsevier
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