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3b2r
From Proteopedia
| 3b2r, resolution 2.07Å () | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Ligands: | |||||||||
| Gene: | PDE5A, PDE5 (Homo sapiens) | ||||||||
| Activity: | 3',5'-cyclic-GMP phosphodiesterase, with EC number 3.1.4.35 | ||||||||
| |||||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||||
Contents |
Crystal Structure of PDE5A1 catalytic domain in complex with Vardenafil
Vardenafil has higher affinity to phosphodiesterase-5 (PDE5) than sildenafil and lower administered dosage for the treatment of erectile dysfunction. However, the molecular basis for these differences is puzzling because two drugs have similar chemical structures. Reported here is a crystal structure of the fully active and nonmutated PDE5A1 catalytic domain in complex with vardenafil. The structure shows that the conformation of the H-loop in the PDE5A1-vardenafil complex is different from those of any known structures of the unliganded PDE5 and its complexes with the inhibitors. In addition, the molecular configuration of vardenafil differs from that of sildenafil when bound to PDE5. It is noteworthy that the binding of vardenafil causes loss of the divalent metal ions that have been observed in all the previously published PDE structures. The conformational variation of both PDE5 and the inhibitors provides structural insight into the different potencies of the drugs.
Conformational variations of both phosphodiesterase-5 and inhibitors provide the structural basis for the physiological effects of vardenafil and sildenafil., Wang H, Ye M, Robinson H, Francis SH, Ke H, Mol Pharmacol. 2008 Jan;73(1):104-10. Epub 2007 Oct 24. PMID:17959709
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
About this Structure
3b2r is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA.
See Also
Reference
- Wang H, Ye M, Robinson H, Francis SH, Ke H. Conformational variations of both phosphodiesterase-5 and inhibitors provide the structural basis for the physiological effects of vardenafil and sildenafil. Mol Pharmacol. 2008 Jan;73(1):104-10. Epub 2007 Oct 24. PMID:17959709 doi:10.1124/mol.107.040212
Categories: 3',5'-cyclic-GMP phosphodiesterase | Homo sapiens | Hengming, K. | Howard, R. | Huanchen, W. | Mengchun, Y. | Sharron, H F. | Allosteric enzyme | Cgmp phosphodiesterase | Cgmp-binding | Hydrolase | Levitratm. | Magnesium | Metal-binding | Nucleotide-binding | Pde5-inhibitor potency | Phosphorylation | Sildenafil | Vardenafil
