First time at Proteopedia? Click on the green links: they change the 3D image. Click and drag the molecules. Proteopedia is a 3D, interactive encyclopedia of proteins, RNA, DNA and other molecules. With a free user account, you can edit pages in Proteopedia. Visit the Main Page to learn more.
1udt
From Proteopedia
| 1udt, resolution 2.30Å () | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Ligands: | , , | ||||||||
| Activity: | 3',5'-cyclic-nucleotide phosphodiesterase, with EC number 3.1.4.17 | ||||||||
| Domains: | PDEase_I | ||||||||
| Related: | 1udu | ||||||||
| |||||||||
| |||||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||||
Crystal structure of Human Phosphodiesterase 5 complexed with Sildenafil(Viagra)
Phosphodiesterases (PDEs) are a superfamily of enzymes that degrade the intracellular second messengers cyclic AMP and cyclic GMP. As essential regulators of cyclic nucleotide signalling with diverse physiological functions, PDEs are drug targets for the treatment of various diseases, including heart failure, depression, asthma, inflammation and erectile dysfunction. Of the 12 PDE gene families, cGMP-specific PDE5 carries out the principal cGMP-hydrolysing activity in human corpus cavernosum tissue. It is well known as the target of sildenafil citrate (Viagra) and other similar drugs for the treatment of erectile dysfunction. Despite the pressing need to develop selective PDE inhibitors as therapeutic drugs, only the cAMP-specific PDE4 structures are currently available. Here we present the three-dimensional structures of the catalytic domain (residues 537-860) of human PDE5 complexed with the three drug molecules sildenafil, tadalafil (Cialis) and vardenafil (Levitra). These structures will provide opportunities to design potent and selective PDE inhibitors with improved pharmacological profiles.
Structure of the catalytic domain of human phosphodiesterase 5 with bound drug molecules., Sung BJ, Hwang KY, Jeon YH, Lee JI, Heo YS, Kim JH, Moon J, Yoon JM, Hyun YL, Kim E, Eum SJ, Park SY, Lee JO, Lee TG, Ro S, Cho JM, Nature. 2003 Sep 4;425(6953):98-102. PMID:12955149
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
About this Structure
1UDT is a 1 chain structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
- Sung BJ, Hwang KY, Jeon YH, Lee JI, Heo YS, Kim JH, Moon J, Yoon JM, Hyun YL, Kim E, Eum SJ, Park SY, Lee JO, Lee TG, Ro S, Cho JM. Structure of the catalytic domain of human phosphodiesterase 5 with bound drug molecules. Nature. 2003 Sep 4;425(6953):98-102. PMID:12955149 doi:10.1038/nature01914
Page seeded by OCA on Tue Feb 17 07:57:41 2009
Categories: 3',5'-cyclic-nucleotide phosphodiesterase | Homo sapiens | Cho, J M. | Eum, S J. | Heo, Y S. | Hwang, K Y. | Hyun, Y L. | Jeon, Y H. | Kim, E. | Kim, J H. | Lee, J I. | Lee, J O. | Lee, T G. | Moon, J. | Park, S Y. | Ro, S. | Sung, B J. | Yoon, J M. | Cgmp-specific phosphodiesterase 5 | Selective inhibitor | Sildenafil
