1udt
From Proteopedia
(New page: 200px<br /> <applet load="1udt" size="450" color="white" frame="true" align="right" spinBox="true" caption="1udt, resolution 2.30Å" /> '''Crystal structure o...) |
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| - | [[Image:1udt.gif|left|200px]]<br /> | + | [[Image:1udt.gif|left|200px]]<br /><applet load="1udt" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="1udt" size=" | + | |
caption="1udt, resolution 2.30Å" /> | caption="1udt, resolution 2.30Å" /> | ||
'''Crystal structure of Human Phosphodiesterase 5 complexed with Sildenafil(Viagra)'''<br /> | '''Crystal structure of Human Phosphodiesterase 5 complexed with Sildenafil(Viagra)'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Phosphodiesterases (PDEs) are a superfamily of enzymes that degrade the | + | 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. |
==About this Structure== | ==About this Structure== | ||
| - | 1UDT is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with ZN, MG and VIA as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/3',5'-cyclic-nucleotide_phosphodiesterase 3',5'-cyclic-nucleotide phosphodiesterase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.4.17 3.1.4.17] Full crystallographic information is available from [http:// | + | 1UDT is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=ZN:'>ZN</scene>, <scene name='pdbligand=MG:'>MG</scene> and <scene name='pdbligand=VIA:'>VIA</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/3',5'-cyclic-nucleotide_phosphodiesterase 3',5'-cyclic-nucleotide phosphodiesterase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.4.17 3.1.4.17] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1UDT OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Cho, J | + | [[Category: Cho, J M.]] |
| - | [[Category: Eum, S | + | [[Category: Eum, S J.]] |
| - | [[Category: Heo, Y | + | [[Category: Heo, Y S.]] |
| - | [[Category: Hwang, K | + | [[Category: Hwang, K Y.]] |
| - | [[Category: Hyun, Y | + | [[Category: Hyun, Y L.]] |
| - | [[Category: Jeon, Y | + | [[Category: Jeon, Y H.]] |
[[Category: Kim, E.]] | [[Category: Kim, E.]] | ||
| - | [[Category: Kim, J | + | [[Category: Kim, J H.]] |
| - | [[Category: Lee, J | + | [[Category: Lee, J I.]] |
| - | [[Category: Lee, J | + | [[Category: Lee, J O.]] |
| - | [[Category: Lee, T | + | [[Category: Lee, T G.]] |
[[Category: Moon, J.]] | [[Category: Moon, J.]] | ||
| - | [[Category: Park, S | + | [[Category: Park, S Y.]] |
[[Category: Ro, S.]] | [[Category: Ro, S.]] | ||
| - | [[Category: Sung, B | + | [[Category: Sung, B J.]] |
| - | [[Category: Yoon, J | + | [[Category: Yoon, J M.]] |
[[Category: MG]] | [[Category: MG]] | ||
[[Category: VIA]] | [[Category: VIA]] | ||
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[[Category: sildenafil]] | [[Category: sildenafil]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:23:23 2008'' |
Revision as of 13:23, 21 February 2008
|
Crystal structure of Human Phosphodiesterase 5 complexed with Sildenafil(Viagra)
Overview
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.
About this Structure
1UDT is a Single protein structure of sequence from Homo sapiens with , and as ligands. Active as 3',5'-cyclic-nucleotide phosphodiesterase, with EC number 3.1.4.17 Full crystallographic information is available from OCA.
Reference
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
Page seeded by OCA on Thu Feb 21 15:23:23 2008
Categories: 3',5'-cyclic-nucleotide phosphodiesterase | Homo sapiens | Single protein | 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. | MG | VIA | ZN | Cgmp-specific phosphodiesterase 5 | Selective inhibitor | Sildenafil
