6l6e

Human PDE5 catalytic core in complex with avanafil

spinqualitylabelsall models 6l6e, resolution 1.92Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6l6e is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.92Å Ligands: E6L, MG, SO4, ZN Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function PDE5A_HUMAN Plays a role in signal transduction by regulating the intracellular concentration of cyclic nucleotides. This phosphodiesterase catalyzes the specific hydrolysis of cGMP to 5'-GMP. Publication Abstract from PubMed 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 alpha-helix, whose contribution to inhibitory potency illustrates the feasibility of exploiting alpha-helix backbone in structure-based drug design. 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.,Hsieh CM, Chen CY, Chern JW, Chan NL J Med Chem. 2020 Aug 13;63(15):8485-8494. doi: 10.1021/acs.jmedchem.0c00853. Epub, 2020 Jul 27. PMID:32663396 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Phosphodiesterase 3D structures

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