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Figure 1.
Figure 1. (a) Monomer of the P7-P6 cleaved Pittsburgh
a[1]-antitrypsin in the classical view with b-sheet A in blue
and the portion of the reactive centre loop which becomes strand
4A after cleavage in red. The normal scissile bond (P1-P1') is
indicated by the arrow. Cleavage at this site results in a full
occupancy of b-sheet A with the inclusion of residues P15
through P3 as s4A. The P7 and P6 residues are indicated and are
separated by 70 Å. The effect of cleavage at P7-P6 is a
partial occupancy of the strand 4A allowing for ready insertion
of the residues C-terminal to the cleavage site, P6*-P3*, from
another monomer. (b) Such intermolecular loop insertion is
demonstrated in the structure of a tetramer extracted from the
infinite polymer, with the P6-P3 segment of one monomer clearly
visible within the b-sheet A of the other. Insertion is in
register with P1-P1' cleaved a[1]-antitrypsin. The monomers
which compose the polymer are related in the crystal by a
2[1]-fold screw axis parallel to the Image cell edge. (c) The
view down the 3[1]-fold screw axis of the crystal lattice
reveals its tube-like nature. The unusually high solvent content
of 73 % is explained by the 108 Å diameter hole that
extends for the length of the crystal. (d) The current model of
the uncleaved a[1]-antitrypsin trimer (magenta) [Elliott et al
1996 and Mahadeva et al 1999] and the structure of the cleaved
a[1]-antitrypsin trimer (cyan) in space-filling representation
after superposition of the first monomer. Polymerisation for the
uncleaved model is affected by in register insertion of the P8
to P3 of the reactive centre loop into the b-sheet A of the
following monomer. The model is thus constrained and cannot
adopt the conformation of the cleaved polymer with which it is
morphologically similar by electron microscopy. The Figures were
generated using Molscript [Kraulis 1991] and Raster3D [Bacon and
Anderson 1988 and Merritt and Murphy 1994].
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