|
|
| Line 1: |
Line 1: |
| [[Image:1xp0.gif|left|200px]] | | {{Seed}} |
| | [[Image:1xp0.png|left|200px]] |
|
| |
|
| <!-- | | <!-- |
| Line 9: |
Line 10: |
| {{STRUCTURE_1xp0| PDB=1xp0 | SCENE= }} | | {{STRUCTURE_1xp0| PDB=1xp0 | SCENE= }} |
|
| |
|
| '''Catalytic Domain Of Human Phosphodiesterase 5A In Complex With Vardenafil'''
| | ===Catalytic Domain Of Human Phosphodiesterase 5A In Complex With Vardenafil=== |
|
| |
|
|
| |
|
| ==Overview==
| | <!-- |
| 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 |
| | (as it appears on PubMed at http://www.pubmed.gov), where 15576036 is the PubMed ID number. |
| | --> |
| | {{ABSTRACT_PUBMED_15576036}} |
|
| |
|
| ==About this Structure== | | ==About this Structure== |
| Line 44: |
Line 48: |
| [[Category: Phosphodiesterase]] | | [[Category: Phosphodiesterase]] |
| [[Category: Vardenafil]] | | [[Category: Vardenafil]] |
| ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 15:19:06 2008'' | | |
| | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 29 02:27:13 2008'' |