6L6E
Human PDE5 catalytic core in complex with avanafil
Summary for 6L6E
| Entry DOI | 10.2210/pdb6l6e/pdb |
| Descriptor | cGMP-specific 3',5'-cyclic phosphodiesterase, 4-[(3-chloranyl-4-methoxy-phenyl)methylamino]-2-[(2S)-2-(hydroxymethyl)pyrrolidin-1-yl]-N-(pyrimidin-2-ylmethyl)pyrimid ine-5-carboxamide, ZINC ION, ... (6 entities in total) |
| Functional Keywords | phosphodiesterase isoform 5, avanafil, enzyme-drug complex, co-crystallization, hydrolase, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor |
| Biological source | Homo sapiens (Human) |
| Total number of polymer chains | 1 |
| Total formula weight | 39660.59 |
| Authors | Hsieh, C.M.,Chan, N.L. (deposition date: 2019-10-28, release date: 2020-09-02, Last modification date: 2023-11-22) |
| Primary citation | Hsieh, C.M.,Chen, C.Y.,Chern, J.W.,Chan, N.L. Structure of Human Phosphodiesterase 5A1 Complexed with Avanafil Reveals Molecular Basis of Isoform Selectivity and Guidelines for Targeting alpha-Helix Backbone Oxygen by Halogen Bonding. J.Med.Chem., 63:8485-8494, 2020 Cited by PubMed Abstract: Phosphodiesterase 5A1 (PDE5) is a key target for treating cardiovascular diseases and erectile dysfunction. Here, we report the crystal structure of PDE5 complexed with the sole second generation drug avanafil. Analysis of protein-drug interactions revealed the structural basis of avanafil's superior isoform selectivity. Moreover, a halogen bonding was observed between avanafil and a backbone carbonyl oxygen of an adjacent α-helix, whose contribution to inhibitory potency illustrates the feasibility of exploiting α-helix backbone in structure-based drug design. PubMed: 32663396DOI: 10.1021/acs.jmedchem.0c00853 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.92 Å) |
Structure validation
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