1udt: Difference between revisions

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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="~~450~~" color="white" frame="true" align="right" spinBox="true"

caption="1udt, resolution 2.30Å" />

'''Crystal structure of Human Phosphodiesterase 5 complexed with Sildenafil(Viagra)'''<br />

==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.

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 [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://~~ispc~~.weizmann.ac.il/oca-bin/ocashort?id=1UDT OCA].

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==

Line 15:

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[[Category: Homo sapiens]]

[[Category: Single protein]]

[[Category: Cho, J.M.]]

[[Category: Cho, J M.]]

[[Category: Eum, S.J.]]

[[Category: Eum, S J.]]

[[Category: Heo, Y.S.]]

[[Category: Heo, Y S.]]

[[Category: Hwang, K.Y.]]

[[Category: Hwang, K Y.]]

[[Category: Hyun, Y.L.]]

[[Category: Hyun, Y L.]]

[[Category: Jeon, Y.H.]]

[[Category: Jeon, Y H.]]

[[Category: Kim, E.]]

[[Category: Kim, J.H.]]

[[Category: Kim, J H.]]

[[Category: Lee, J.I.]]

[[Category: Lee, J I.]]

[[Category: Lee, J.O.]]

[[Category: Lee, J O.]]

[[Category: Lee, T.G.]]

[[Category: Lee, T G.]]

[[Category: Moon, J.]]

[[Category: Park, S.Y.]]

[[Category: Park, S Y.]]

[[Category: Ro, S.]]

[[Category: Sung, B.J.]]

[[Category: Sung, B J.]]

[[Category: Yoon, J.M.]]

[[Category: Yoon, J M.]]

[[Category: MG]]

[[Category: VIA]]

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[[Category: sildenafil]]

''Page seeded by [http://~~ispc~~.weizmann.ac.il/oca OCA ] on ~~Mon Nov 12 19~~:33:~~35 2007~~''

''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:23:23 2008''

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@@ Line 1: / Line 1: @@
-[[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="450" color="white" frame="true" align="right" spinBox="true"
 caption="1udt, resolution 2.30&Aring;" />
 '''Crystal structure of Human Phosphodiesterase 5 complexed with Sildenafil(Viagra)'''<br />
 ==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.
+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==
-UDT 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://ispc.weizmann.ac.il/oca-bin/ocashort?id=1UDT OCA].
+UDT 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==
@@ Line 15: / Line 14: @@
 [[Category: Homo sapiens]]
 [[Category: Single protein]]
-[[Category: Cho, J.M.]]
+[[Category: Cho, J M.]]
-[[Category: Eum, S.J.]]
+[[Category: Eum, S J.]]
-[[Category: Heo, Y.S.]]
+[[Category: Heo, Y S.]]
-[[Category: Hwang, K.Y.]]
+[[Category: Hwang, K Y.]]
-[[Category: Hyun, Y.L.]]
+[[Category: Hyun, Y L.]]
-[[Category: Jeon, Y.H.]]
+[[Category: Jeon, Y H.]]
 [[Category: Kim, E.]]
-[[Category: Kim, J.H.]]
+[[Category: Kim, J H.]]
-[[Category: Lee, J.I.]]
+[[Category: Lee, J I.]]
-[[Category: Lee, J.O.]]
+[[Category: Lee, J O.]]
-[[Category: Lee, T.G.]]
+[[Category: Lee, T G.]]
 [[Category: Moon, J.]]
-[[Category: Park, S.Y.]]
+[[Category: Park, S Y.]]
 [[Category: Ro, S.]]
-[[Category: Sung, B.J.]]
+[[Category: Sung, B J.]]
-[[Category: Yoon, J.M.]]
+[[Category: Yoon, J M.]]
 [[Category: MG]]
 [[Category: VIA]]
@@ Line 38: / Line 37: @@
 [[Category: sildenafil]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 19:33:35 2007''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:23:23 2008''