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Figure 2.
Fig. 2. Structural similarities between human topo I and HP1
integrase. (A) The sequence and secondary structural elements of
reconstituted human topo I are indicated in the standard
coloring scheme of the domain architecture of the enzyme (Fig.
1A), and^ the structurally similar regions of HP1 integrase are
shown in red with gray background. Catalytically relevant
residues of human topo I are highlighted in cyan, and the
positions of known CPT-resistant mutations in human, hamster,
and yeast topoisomerases I are shown in gray.  -Helices
18 and 19 are not depicted because these correspond^ to the
linker domain (20), which is not present in the reconstituted^
enzyme. (B) Stereoview of the superposition of core subdomain
III (red) and the COOH-terminal domain (green) of human topo I
and bacteriophage HP1 integrase (gray) (38). The active-site^
residues of each enzyme are shown, with the human topo I
residues in cyan and the integrase residues in gray. Helices 8,
10, 15, and 17 of core subdomain III of topo I are also
indicated. There^ is no structural equivalent in the integrase
for the topo I COOH-terminal domain past the first eight
residues, which contain the catalytic^ Tyr723. The C positions
of the active-site residues Arg488 and Arg590 of topo I (20)
superimpose within 0.6 and 1.9 Å, respectively, of the C
positions
of Arg207 and Arg283 in the integrase. His306 of the integrase
superimposes within 3.3 Å on His632 of human topo I, but
the putative catalytic His280 of the integrase superimposes on a
noncatalytic residue of human topo I, Lys587. Abbreviations for
the amino acid residues are as follows: A, Ala; C, Cys; D, Asp;
E, Glu; F, Phe; G, Gly; H, His; I, Ile; K, Lys; L, Leu; M, Met;
N, Asn; P, Pro; Q, Gln; R, Arg; S, Ser; T, Thr; V, Val; W, Trp;
and Y, Tyr.
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