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Figure 2.
Figure 2. The Conserved Glutamine Is the Primary
Selectivity Switch that Confers Nucleotide Specificity to
PDEsThe protein ribbons for PDE1B, PDE4D, and PDE5A are
represented by red, blue, and green, respectively. The
ball-and-stick representation of protein side chains and
nucleotides follows the same color scheme as in Figure 1. (A)
Q369 recognizing AMP in PDE4D. Q369 forms a bidentate H-bond
with the adenine moiety. Specifically, the Nε atom of Q369
donates an H-bond to the N1 atom of the adenine ring and the Oε
accepts a H-bond from N6 in the exocyclic amino group of
adenine. This particular orientation of Q369 is stabilized by
H-bonding of Oε to the phenolic hydroxyl Oη of Y329. In
addition, N321 forms a bidentate H-bond with the adenine base by
donating one H-bond from Nδ to N7 of the adenine base and
accepting one H-bond from the N6 of the exocyclic amino group to
its Oδ. (B) Q817 recognizing GMP in PDE5A. Q817 forms a
bidentate H-bond with GMP. The particular orientation of the
Q817 side chain is anchored by its H-bond interaction with Q775.
The orientation of Q775 side chain is in turn anchored by the
H-bond between Nε in Q775 and the carbonyl oxygen in A767 and
the H-bond between Oε of Q775 and the Nε of W853. (C) Q421
recognizing AMP in the model of AMP bound to PDE1B. (D) Q421
recognizing GMP in the model of GMP bound to PDE1B. In (C) and
(D), there are no supporting residues to anchor the orientation
of the key glutamine residue.
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