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Figure 3.
Figure 3. The Molecular Brake at the Kinase Hinge Region of
FGFR2K Regulates the Kinase Activation and Is Disengaged Either
by A Loop Tyrosine Phosphorylation or Directly by the Pathogenic
Mutations
(A) In the unphosphorylated wild-type structure,
residues N549, E565, and K641 form a network of hydrogen bonds
in the kinase hinge region, which serves as a molecular brake to
keep the enzyme in an inactive state.
(B) The molecular
brake is disengaged in the A loop tyrosine phosphorylated
wild-type FGFR2K structure. This molecular brake is also
disengaged in the unphosphorylated mutant FGFR2K structures
(C–G). To assist the readers, the whole unphosphorylated
wild-type FGFR2K structure is also shown in cartoon and solid
semitransparent surface, and the kinase hinge region is boxed.
Atom colorings are as follows: oxygens in red, nitrogens in
blue, and carbons are colored according to the kinase region to
which they belong. The kinase hinge, the αC-β4 loop (shown in
sticks in [A]–[G]), and β8 strand are colored green, wheat,
and cyan, respectively. The rest of the N lobe and C lobe is
colored light purple and light blue, respectively. The three
critical hydrogen bonds between N549 and the backbone atoms of
αC-β4 loop are highlighted by red dashed lines. The remaining
hydrogen bonds are shown as black dashed lines.
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