1udu: Difference between revisions

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Revision as of 15:30, 20 March 2008

File:1udu.gif

, resolution 2.83Å

Ligands:

, and

Activity:

3',5'-cyclic-nucleotide phosphodiesterase, with EC number 3.1.4.17

Coordinates:

save as pdb, mmCIF, xml

Crystal structure of Human Phosphodiesterase 5 complexed with tadalafil(Cialis)

OverviewOverview

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 StructureAbout this Structure

1UDU is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

ReferenceReference

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 Mar 20 14:30:41 2008

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OCA

@@ Line 1: / Line 1: @@
-[[Image:1udu.gif|left|200px]]<br /><applet load="1udu" size="350" color="white" frame="true" align="right" spinBox="true"
+[[Image:1udu.gif|left|200px]]
-caption="1udu, resolution 2.83&Aring;" />
-'''Crystal structure of Human Phosphodiesterase 5 complexed with tadalafil(Cialis)'''<br />
+ {{Structure
+|PDB= 1udu |SIZE=350|CAPTION= <scene name='initialview01'>1udu</scene>, resolution 2.83&Aring;
+|SITE=
+|LIGAND= <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene> and <scene name='pdbligand=CIA:6-BENZO[1,3]DIOXOL-5-YL-2-METHYL-2,3,6,7,12,12A-HEXAHYDRO-PYRAZINO[1',2':1,6]PYRIDO[3,4-B]INDOLE-1,4-DIONE'>CIA</scene>
+|ACTIVITY= [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]
+|GENE=
+}}
+'''Crystal structure of Human Phosphodiesterase 5 complexed with tadalafil(Cialis)'''
 ==Overview==
@@ Line 7: / Line 16: @@
 ==About this Structure==
-UDU 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=CIA:'>CIA</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=1UDU OCA].
+UDU is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1UDU 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:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=12955149 12955149]
+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:[http://www.ncbi.nlm.nih.gov/pubmed/12955149 12955149]
 [[Category: 3',5'-cyclic-nucleotide phosphodiesterase]]
 [[Category: Homo sapiens]]
@@ Line 37: / Line 46: @@
 [[Category: tadalafil]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:23:23 2008''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 14:30:41 2008''