Figure 2.
Figure 2. Crystal structures reveal a novel allosteric site in
PTP1B. (a) Inhibitor 2 (spheres) binds in a groove formed by
helices 3
and 6
that positions the catalytically important WPD loop. Distance
from the active site Cys is 20
Å. (b) Compound 2 binds in a hydrophobic pocket formed by
Leu192, Phe196 and Phe280. Hydrogen bonds with side chains of
Glu276, Asn193 and the main chain carbonyl of Phe196
(water-mediated) are shown. (c) Overlay of the crystal
structures of compounds 1 (orange, 2.2-Å resolution), 2 (yellow,
1.9-Å resolution) and 3 (blue sticks and mesh, 2.7 Å
resolution). The benzofuran core of the three compounds occupies
the same hydrophobic site. Allosteric inhibitors progressively
wrap around Phe280, correlating with increasing potency. PTP1B
and the side chain of Phe280 are gray. This figure was created
using PyMOL (DeLano Scientific; http://www.pymol.org).
The above figure is reprinted
by permission from Macmillan Publishers Ltd:
Nat Struct Mol Biol
(2004,
11,
730-737)
copyright 2004.
3
and 
20
Å. (b) Compound 2 binds in a hydrophobic pocket formed by
Leu192, Phe196 and Phe280. Hydrogen bonds with side chains of
Glu276, Asn193 and the main chain carbonyl of Phe196
(water-mediated) are shown. (c) Overlay of the crystal
structures of compounds 1 (orange, 2.2-Å resolution), 2 (yellow,
1.9-Å resolution) and 3 (blue sticks and mesh, 2.7 Å
resolution). The benzofuran core of the three compounds occupies
the same hydrophobic site. Allosteric inhibitors progressively
wrap around Phe280, correlating with increasing potency. PTP1B
and the side chain of Phe280 are gray. This figure was created
using PyMOL (DeLano Scientific; http://www.pymol.org).