Figure 3.
(a) cSrc in complex with the type III inhibitor 1b. (b) cSrc
in complex with the type III inhibitor 1c. Electron density maps
(2F[o] – F[c]) of cSrc (gray) and 1b, 1c (red) are contoured
at 1 .
Hydrogen bonding interactions of the inhibitor with helix C
(blue) and the backbone of the DFG motif (orange) stabilize the
inhibitor in the allosteric site and are highlighted by dotted
lines (red). The hinge region (pink) of the kinase domain
(represented by Met341) is not contacted by either inhibitor.
(c) Alignment of the cSrc–1c complex with BIRB-796 bound to
p38 (yellow)
(Protein Data Bank code 1KV2). Hydrogen bonds of the p38 –BIRB-796
complex are highlighted by dotted lines (red). The pyrazolourea
moiety of both ligands resides in the allosteric site, and the
naphthyl side chain is located in the hydrophobic subpocket
close to the gatekeeper residue (Thr106 in p38 and
Thr338 in cSrc). The morpholino group of BIRB-796 binds to the
hinge region of p38 .
Although the binding mode of the aryl pyrazolourea scaffold is
conserved in both complexes, BIRB-796 binds only weakly to cSrc
with a K[d] > 10 M.
Coordinates and structure factors have been deposited under the
following Protein Data Bank accession codes: cSrc bound to 1b,
3F3U; cSrc bound to 1c, 3F3T.
.
Hydrogen bonding interactions of the inhibitor with helix C
(blue) and the backbone of the DFG motif (orange) stabilize the
inhibitor in the allosteric site and are highlighted by dotted
lines (red). The hinge region (pink) of the kinase domain
(represented by Met341) is not contacted by either inhibitor.
(c) Alignment of the cSrc–1c complex with BIRB-796 bound to
p38 
(yellow)
(Protein Data Bank code 1KV2). Hydrogen bonds of the p38 
M.
Coordinates and structure factors have been deposited under the
following Protein Data Bank accession codes: cSrc bound to 1b,
3F3U; cSrc bound to 1c, 3F3T.