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PDBsum entry 1asu
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DNA integration
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PDB id
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1asu
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References listed in PDB file
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Key reference
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Title
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High-Resolution structure of the catalytic domain of avian sarcoma virus integrase.
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Authors
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G.Bujacz,
M.Jaskólski,
J.Alexandratos,
A.Wlodawer,
G.Merkel,
R.A.Katz,
A.M.Skalka.
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Ref.
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J Mol Biol, 1995,
253,
333-346.
[DOI no: ]
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PubMed id
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Abstract
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Retroviral integrase (IN) functions to insert retroviral DNA into the host cell
chromosome in a highly coordinated manner. IN catalyzes two biochemically
separable reactions: processing of the viral DNA ends and joining of these ends
to the host DNA. Previous studies suggested that these two reactions are
chemically similar and are carried out by a single active site that is
characterized by a highly conserved constellation of carboxylate residues, the
D,D(35)E motif. We report here the crystal structure of the isolated catalytic
domain of avian sarcoma virus (ASV) IN, solved using multiwavelength anomalous
diffraction data for a selenomethionine derivative and refined at 1.7 A
resolution. The protein is a crystallographic dimer with each monomer featuring
a five-stranded mixed beta-sheet region surrounded by five alpha-helices. Based
on the general fold and the arrangement of catalytic carboxylate residues, it is
apparent that ASV IN is a member of a superfamily of proteins that also includes
two types of nucleases, RuvC and RNase H. The general fold and the dimer
interface are similar to those of the analogous domain of HIV-1 IN, whose
crystal structure has been determined at 2.5 A resolution. However, the ASV IN
structure is more complete in that all three critical carboxylic acids, Asp64,
Asp121 and Glu157, are ordered. The ordered active site and the considerably
higher resolution of the present structure are all important to an understanding
of the mechanism of retroviral DNA integration, as well as for designing
antiviral agents that may be effective against HIV.
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Figure 1.
Figure 1. Primary structure of retroviral integrase. A, Representation of ASV IN showing the three functional domains
and indicating the fragment included in the domain analyzed in this investigation. B, Alignment of the amino acid
sequences in the ASV andHIV-1IN catalytic domains, with the elements of secondary structure indicated. Residues shown
in red are identical, those shown in blue are of similar type. The sequence with a broken underline was not observed in
the crystal structure of HIV-1 IN.
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Figure 5.
Figure 5. Stereoviews of the dimers of the catalytic domain of IN generated using O (Jones & Kjeldgaard, 1994). A, A
dimer of the ASV IN core domain viewed along its 2-fold axis, with Wat450 positions marked as blue spheres. B,
Superposition of the main chains of ASV and HIV-1 IN core domains. The superposition is based on the best fit between
the C
a
atoms of the blue (ASV) and gold (HIV-1) chains. The green (ASV) and red (HIV-1) subunits (generated by the
corresponding molecular dyads) show considerable deviations.
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The above figures are
reprinted
by permission from Elsevier:
J Mol Biol
(1995,
253,
333-346)
copyright 1995.
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