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Figure 1.
Figure 1. Classification of the Active Site of PDEs(A) The
active site of PDEs is divided into three pockets: the metal
binding pocket (M) shown in blue, the purine-selective glutamine
and hydrophobic clamp pocket (Q) shown in red (which is further
divided into Q[1] and Q[2] subpockets), and the solvent-filled
side pocket (S) shown in green. This color coding of the active
site pocket is mapped on the surface of PDE4B in complex with
cilomilast, which is shown as a stick model bound at the active
site. The cocrystal structure of PDE4B in complex with
cilomilast has also been used to display the surfaces in
(B)-(D).(B) Same as (A), but a view of the PDE active site
looking toward the S pocket. This view is a clockwise rotation
of about 90° along the length of cilomilast from the view in
Figure 1A. The subpockets that subdivide the Q pocket are also
labeled: Q[1] is the small subpocket, and Q[2] is the large
subpocket.(C) Same as (A), but a view of the PDE active site
looking away from the S pocket. This view is a counterclockwise
rotation of about 90° along the length of cilomilast from the
view in Figure 1A. All the subpockets are labeled.(D) Residues
lining the three active site pockets. The active site surface is
semitransparent to reveal residues that make up the active site.
The absolutely conserved residues in all PDEs are colored blue.
Residues conserved in both cAMP- and cGMP-specific PDEs are
colored green. The other variable residues are colored red.
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