3HMV
Catalytic domain of human phosphodiesterase 4B2B in complex with a tetrahydrobenzothiophene inhibitor
Summary for 3HMV
| Entry DOI | 10.2210/pdb3hmv/pdb |
| Descriptor | cAMP-specific 3',5'-cyclic phosphodiesterase 4B, ZINC ION, MAGNESIUM ION, ... (6 entities in total) |
| Functional Keywords | pde, phosphodiesterase, camp, alternative splicing, hydrolase, phosphoprotein, polymorphism |
| Biological source | Homo sapiens (human) |
| Total number of polymer chains | 2 |
| Total formula weight | 87862.03 |
| Authors | Somers, D.O.,Neu, M. (deposition date: 2009-05-29, release date: 2010-06-09, Last modification date: 2024-04-03) |
| Primary citation | Kranz, M.,Wall, M.,Evans, B.,Miah, A.,Ballantine, S.,Delves, C.,Dombroski, B.,Gross, J.,Schneck, J.,Villa, J.P.,Neu, M.,Somers, D.O. Identification of PDE4B Over 4D subtype-selective inhibitors revealing an unprecedented binding mode Bioorg.Med.Chem., 17:5336-5341, 2009 Cited by PubMed Abstract: A PDE4B over 4D-selective inhibitor programme was initiated to capitalise on the recently discovered predominance of the PDE4B subtype in inflammatory cell regulation. The SAR of a tetrahydrobenzothiophene (THBT) series did not agree with either of two proposed docking modes in the 4B binding site. A subsequent X-ray co-crystal structure determination revealed that the THBT ligand displaces the Gln-443 residue, invariably ligand-anchoring in previous PDE4 co-crystal structures, and even shifts helix-15 by 1-2A. For the first time, several residues of the C-terminus previously proposed to be involved in subtype selectivity are resolved and three of them extend into the ligand binding site potentially allowing for selective drug design. PubMed: 19525117DOI: 10.1016/j.bmc.2009.03.061 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.23 Å) |
Structure validation
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