1q9m | pdb_00001q9m
Three dimensional structures of PDE4D in complex with roliprams and implication on inhibitor selectivity
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Overview
Selective inhibitors against the 11 families of cyclic nucleotide, phosphodiesterases (PDEs) are used to treat various human diseases. How, the inhibitors selectively bind the conserved PDE catalytic domains is, unknown. The crystal structures of the PDE4D2 catalytic domain in complex, with (R)- or (R,S)-rolipram suggest that inhibitor selectivity is, determined by the chemical nature of amino acids and subtle conformational, changes of the binding pockets. The conformational states of Gln369 in, PDE4D2 may play a key role in inhibitor recognition. The corresponding, Y329S mutation in PDE7 may lead to loss of the hydrogen bonds between, rolipram and Gln369 and is thus a possible reason explaining PDE7's, insensitivity to rolipram inhibition. Docking of the PDE5 inhibitor, sildenafil into the PDE4 catalytic pocket further helps understand, inhibitor selectivity.
Disease
Known disease associated with this structure: Stroke, susceptibility to, 1 OMIM:[600129]
About this Structure
1Q9M is a Single protein structure of sequence from Homo sapiens with ZN and ROL as ligands. This structure superseeds the now removed PDB entry 1OYM. Active as 3',5'-cyclic-nucleotide phosphodiesterase, with EC number 3.1.4.17 Full crystallographic information is available from OCA.
Reference
Three-dimensional structures of PDE4D in complex with roliprams and implication on inhibitor selectivity., Huai Q, Wang H, Sun Y, Kim HY, Liu Y, Ke H, Structure. 2003 Jul;11(7):865-73. PMID:12842049
Page seeded by OCA on Fri Feb 15 16:43:15 2008
