1. The Division of Drug Discovery, CrystalGenomics, Inc., Daedeok Biocommunity, Jeonmin-dong, Yuseong-gu, Daejeon, 305-390, South Korea
2. Protein Design Laboratory, Yokohama City University, 1-7-29 Suehiro-cho, Tsurumi, Yokohama 230-0045, Japan
3. Department of Chemistry, Korea Advanced Institute of Science and Technology, 373-1 Kusong-dong, Yuseong-gu, Daejeon 305-701, South Korea
4. These authors contributed equally to this work

Correspondence to: Kwang Yeon Hwang^1,4Seonggu Ro¹ Email: sgro@crystalgenomics.com
Email: jmcho@crystalgenomics.com
Coordinates for the sildenafil, tadalafil and vardenafil complex structure have been deposited in the Protein Data Bank under accession codes 1UDT, 1UDU and 1UHO, respectively.

Phosphodiesterases (PDEs) are a superfamily of enzymes that degrade the intracellular second messengers cyclic AMP and cyclic GMP^{1, 2, 3}. 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^{4, 5, 6, 7}. 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^{8, 9}. 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.