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Figure 1.
FIGURE 1. A-C, surface rendering of the pore of entry to
the Na^+ binding site of human thrombin in the structure 1SG8
(15) (A) when compared with the same region in murine thrombin
(B) and the thrombin chimera (C). Residues lining the pore are
color-coded according to their physical properties (red =
positively charged, blue = negatively charged, orange =
hydrophobic, white = all others). In the human enzyme, the pore
is defined by residue Asp-222 in the 220-loop and the sequence
PDEGKR from Pro-186 to Arg-187 in the 186-loop (Table 1) (A). In
murine thrombin (B), residue 222 is Lys, and the corresponding
sequence in the 186-loop is VNDTKR (Table 1). The side chain of
Lys-222 completely occludes the pore. The side chain of Asn-186a
is glycosylated (NAG). Occlusionofthe pore is also seen in the
thrombin chimera (C), in which the human enzyme carries all
residues around the pore as in murine thrombin. There is no
glycosylation of Asn-186a in the chimera. D-F, architecture of
the pore of entry to the Na^+ binding site in the same
orientation as shown in the surface rendering (A-C), with
relevant residues rendered in Corey-Pauling-Koltun model (carbon
in yellow) and the 2F[o] - F[c] electron density maps contoured
at the 0.7  level for the
structures presented in this study (E and F). The human enzyme
(D) shows the pore wide open, whereas Lys-222 in murine thrombin
(E) occludes the pore and positions the N  atom within H-bonding
distance from Lys-185, Asp-186b, and Lys-186d. The backbone
oxygen atom of residue 186b is flipped relative to the position
assumed in the fast form of the human enzyme. Also shown is the
indole side chain of Trp-20, which is Ser in human thrombin, as
a structural signature of the murine enzyme. Lys-222 in the
thrombin chimera (F) is positioned as in the murine thrombin
structure.
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