10OZ
Structure of PDE5 PDE6 chimera
Summary for 10OZ
| Entry DOI | 10.2210/pdb10oz/pdb |
| EMDB information | 75366 |
| Descriptor | cGMP-specific 3',5'-cyclic phosphodiesterase PDE5-PDE6 chimera, Retinal rod rhodopsin-sensitive cGMP 3',5'-cyclic phosphodiesterase subunit gamma, 5-{2-ETHOXY-5-[(4-METHYLPIPERAZIN-1-YL)SULFONYL]PHENYL}-1-METHYL-3-PROPYL-1H,6H,7H-PYRAZOLO[4,3-D]PYRIMIDIN-7-ONE, ... (6 entities in total) |
| Functional Keywords | phosphodiesterase, hydrolase |
| Biological source | Bos taurus (domestic cattle) More |
| Total number of polymer chains | 4 |
| Total formula weight | 208961.99 |
| Authors | |
| Primary citation | Srivastava, D.,Singh, S.,Yu, C.,Boyd, K.,Artemyev, N.O. Structural basis of phosphodiesterase-5 conformational organization revealed by a PDE6/PDE5 Chimera. J.Biol.Chem., :111467-111467, 2026 Cited by PubMed Abstract: Phosphodiesterase 5 (PDE5) plays critical role in the nitric oxide-cGMP signaling pathway. Consequently, PDE5 catalytic site inhibitors are widely used in the treatment of erectile dysfunction and pulmonary arterial hypertension. Despite a wealth of structural data on the individual PDE5 catalytic domain with bound drug molecules, understanding of the structural organization of the full-length enzyme and its allosteric activation by noncatalytic cGMP-binding is lacking. To begin to understand the structural organization of PDE5, we solved a cryo-EM structure of a chimeric PDE enzyme (PDE6C/5) comprised of the regulatory domains of cone PDE6C and the PDE5 catalytic domain. The PDE6C/5 structure revealed the protein in the open state conformation similar to that of PDE6, suggesting a comparable conformation for the cGMP-bound PDE5 molecule. The H- and M-loops outlying the catalytic pocket, which are conformationally variable in the structures of isolated PDE5 catalytic domain, are immobilized in the PDE6/5 chimera via the interaction of the H-loop with a linker helix LH2. Decreased dynamics of these loops may underlie the higher catalytic activities of the full-length PDE5 and PDE6C/5 compared to that of the isolated PDE5 catalytic domain. Furthermore, the PDE6C/5 structure defines the folding requirement of the PDE6 catalytic domain for chaperone-dependent maturation that is important for vision. PubMed: 42001945DOI: 10.1016/j.jbc.2026.111467 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3.06 Å) |
Structure validation
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