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Figure 3.
Figure 3. Stereo views of structures of the blocking
peptides. (a) The lower half of the A-sheet (red) of the ternary
complex of antithrombin showing the exogenous tetrapeptide WMDF
(Trp-Met-Asp-Phe) in the hydrophobic enclosure formed by helix F
and strands 3 and 5 of the A-sheet. Sigma a weighted 2F[0]-F[c]
map contoured at one-times the rmsd of the map showing the
tetrapeptide anchored by the insertion of the Met and Phe
side-chains into the P6 and P4 positions of the sheet. (b)
Detailed interactions of WMDF. The tetrapeptide (ball and stick)
is coloured in pink and the P14-9 (ball and stick) peptide in
yellow. Helix F and its connecting loop to s3A are superimposed
with those of latent antithrombin (green) showing the movement
of the connecting loop caused by the burial of the bulky Trp
side-chain. Some of the residues (F368, I202 and I213) involved
in forming hydrophobic interactions with the peptide are shown.
(c) Structure of the P14-P9 antithrombin complex with the
tripeptide formyl-Met-Leu-Phe binding to the lower half of the
A-sheet in the P6-P4 position. The peptide forms six hydrogen
bonds with adjacent main chain residues. The Met and Phe of the
tripeptide with internally inserted side-chains are anchored at
P6 and P4 positions, respectively, which is almost identical to
the equivalent residues of the tetrapeptide WMDF. The P8
position above the peptide is occupied by a single glycerol
molecule (ball and stick in green) that H-bonds to His334 in
s5A, reforming the normal H-bond network of the six-stranded
A-sheet formed by H334 and P8 Thr (Figure 4a). Nitrogen atoms
are shown in blue, carbon atoms in black and oxygen atoms in
red. Hydrogen bonds are shown as cyan broken lines.
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