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Figure 3.
Figure 3: The colchicine-binding site on tubulin. a,
DAMA-colchicine superimposed on electron-density maps. The 3.5 Å
F[obs]-F[calc] omit map (cyan) is contoured at 3 .
The 4 Å F[obs]-F[calc] maps calculated with colchicine (red,
contoured at 3 )
and with DAMA-colchicine but F[obs] of a
tubulin-colchicine:RB3-SLD complex (green, contoured at -3.3
)
are also presented. b, The colchicine site in the
tubulin-colchicine:RB3-SLD complex (bright colours: tubulin
loops and secondary structure elements contacting colchicine).
c, Interference between colchicine binding and the straight
conformation of tubulin in protofilaments. An subunit
is positioned near a colchicine-bound subunit
as across an intradimer longitudinal contact in a protofilament.
The -tubulin
subunit is prevented from occupying this position because of:
(1) steric hindrance between colchicine and residues 101,
181
and GTP; and (2) colchicine forcing the T7 loop, H8 helix (for
clarity, only side chains of two interfering residues-- 71
and 251--are
presented) and the Lys 352
side chain to interfere with -tubulin.
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