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Figure 1.
Figure 1. Crystal Structures of PDE1B, PDE4B, PDE4D, and
PDE5A in Complex with AMP or GMPThe overall structures of PDE1B,
PDE4B, PDE4D, and PDE5A are represented by ribbon diagrams
colored red, cyan, blue, and green, respectively. Zinc and
magnesium ions are represented by yellow and magenta spheres,
respectively. This color scheme is used throughout the figures
of this report. (A)–(D) have the same view looking down the
nucleotide binding pocket for ready comparison. The sixteen
helices are labeled in all four PDEs. In each case, positions of
all 17 invariant residues are highlighted in yellow. (E)–(G)
have the same zoom-in view of the active site. (A) PDE1B
apo-structure. (B) PDE4B in complex with AMP. Conventional
atomic color coding is used to represent AMP except carbon atoms
are colored green. (C) PDE4D in complex with AMP. (D) PDE5A
chimera in complex with GMP. Conventional atomic color coding is
used to represent GMP except carbon atoms are colored yellow.
(E) Superposition of PDE4B+AMP, PDE4D+AMP, and PDE5A+GMP show
conserved binding mode of nucleotides. The PDE nucleotide
binding site can be divided into four regions: nucleotide
recognition, hydrophobic clamp, metal binding, and hydrolysis.
(F) Overlay of PDE4D with AMP or Rolipram reveals conserved
binding interactions. (G) Overlay of PDE5A with GMP or
Sildenafil reveals conserved binding interactions. The
pyrazolopyrimidinone group of Sildenafil mimics the guanine in
GMP and they overlap in space. They both are sandwiched by the
hydrophobic clamp and also make the same bidentate H-bonds with
the conserved Q817.
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