6F8X
Crystal structure of the PDE4D catalytic domain in complex with GEBR-26g
Summary for 6F8X
| Entry DOI | 10.2210/pdb6f8x/pdb |
| Descriptor | cAMP-specific 3',5'-cyclic phosphodiesterase 4D, ZINC ION, MAGNESIUM ION, ... (7 entities in total) |
| Functional Keywords | pde4, catalytic domain, inhibitor, gebr, hydrolase |
| Biological source | Homo sapiens (Human) |
| Cellular location | Apical cell membrane : Q08499 |
| Total number of polymer chains | 2 |
| Total formula weight | 80493.14 |
| Authors | Prosdocimi, T.,Donini, S.,Parisini, E. (deposition date: 2017-12-13, release date: 2018-05-16, Last modification date: 2024-01-17) |
| Primary citation | Prosdocimi, T.,Mollica, L.,Donini, S.,Semrau, M.S.,Lucarelli, A.P.,Aiolfi, E.,Cavalli, A.,Storici, P.,Alfei, S.,Brullo, C.,Bruno, O.,Parisini, E. Molecular Bases of PDE4D Inhibition by Memory-Enhancing GEBR Library Compounds. Biochemistry, 57:2876-2888, 2018 Cited by PubMed Abstract: Selected members of the large rolipram-related GEBR family of type 4 phosphodiesterase (PDE4) inhibitors have been shown to facilitate long-term potentiation and to improve memory functions without causing emetic-like behavior in rodents. Despite their micromolar-range binding affinities and their promising pharmacological and toxicological profiles, few if any structure-activity relationship studies have been performed to elucidate the molecular bases of their action. Here, we report the crystal structure of a number of GEBR library compounds in complex with the catalytic domain of PDE4D as well as their inhibitory profiles for both the long PDE4D3 isoform and the catalytic domain alone. Furthermore, we assessed the stability of the observed ligand conformations in the context of the intact enzyme using molecular dynamics simulations. The longer and more flexible ligands appear to be capable of forming contacts with the regulatory portion of the enzyme, thus possibly allowing some degree of selectivity between the different PDE4 isoforms. PubMed: 29652483DOI: 10.1021/acs.biochem.8b00288 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.95 Å) |
Structure validation
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