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| {{STRUCTURE_1xon| PDB=1xon | SCENE= }} | | {{STRUCTURE_1xon| PDB=1xon | SCENE= }} |
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| '''Catalytic Domain Of Human Phosphodiesterase 4D In Complex With Piclamilast'''
| | ===Catalytic Domain Of Human Phosphodiesterase 4D In Complex With Piclamilast=== |
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| ==Overview==
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| Phosphodiesterases (PDEs) comprise a large family of enzymes that catalyze the hydrolysis of cAMP or cGMP and are implicated in various diseases. We describe the high-resolution crystal structures of the catalytic domains of PDE4B, PDE4D, and PDE5A with ten different inhibitors, including the drug candidates cilomilast and roflumilast, for respiratory diseases. These cocrystal structures reveal a common scheme of inhibitor binding to the PDEs: (i) a hydrophobic clamp formed by highly conserved hydrophobic residues that sandwich the inhibitor in the active site; (ii) hydrogen bonding to an invariant glutamine that controls the orientation of inhibitor binding. A scaffold can be readily identified for any given inhibitor based on the formation of these two types of conserved interactions. These structural insights will enable the design of isoform-selective inhibitors with improved binding affinity and should facilitate the discovery of more potent and selective PDE inhibitors for the treatment of a variety of diseases.
| | The line below this paragraph, {{ABSTRACT_PUBMED_15576036}}, adds the Publication Abstract to the page |
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| | {{ABSTRACT_PUBMED_15576036}} |
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| ==About this Structure== | | ==About this Structure== |
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| [[Category: Phosphodiesterase]] | | [[Category: Phosphodiesterase]] |
| [[Category: Piclamilast]] | | [[Category: Piclamilast]] |
| ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 15:18:10 2008'' | | |
| | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 16:57:27 2008'' |
