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Figure 10.
Figure 10. Surface representation of HNF-p1w dimer and L12H
homology model. (a) Electrostatic potential of the DCoH-binding
surface of HNF-p1w (stereo pair). The coloring code is red, <
-10 kT/e; white, -10kT/e to 10kT/e; and blue, >10kT/e. Residues
E11 and E18 are involved in ion-pair interactions with DCoH
residues.[35] The exposed concave surface is complementary in
shape to the top of the DCoH saddle as predicted by model
building studies (see the text) and observed in the recent
co-crystal structure. [35] (b) The DCoH-binding surface of
HNF-p1w dimer has a leucine-rich stripe (leucine residues 5, 8,
12, 13, 16 and 21, and their symmetry-related residues) shown in
green. The orientation of molecular surface (white) of the
HNF-p1w dimer is same as in (a). L12 is located in the middle of
the leucine-rich stripe. Residues 1-4 and 1'-4' have been
omitted for clarity. (c)-(e) Homology model of the L12H variant
dimer. (c) The variant side-chain is compatible with a native
overall main-chain fold. One protomer is shown in cyan and the
other in red; terminal residues 1-4 and 1'-4' are disordered in
accord with NMR evidence of flexibility. (d) The structure of
the mini-zipper is predicted to accommodate a pair of histidine
side-chains (yellow) with exposure of polar N  epsilon
ring protons. Neighboring side-chains are in positions similar
to those in crystal structure. (e) The surface of the variant
mini-zipper is predicted to contain a weakly polar protuberance
(yellow) due to the edges of the two His side-chains. This
change in surface character would be expected to perturb DCoH
binding. (a), (b) and (e) Generated using the program GRASP;[85]
(c) and (d) (and other Figures) were made using InsightII (MSI,
Inc., San Diego).
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