1udu

File:1udu.gif

spinqualitylabelsall models 1udu, resolution 2.83Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

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 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.

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 Feb 21 15:23:23 2008