3LXG
Crystal structure of rat phosphodiesterase 10A in complex with ligand WEB-3
Summary for 3LXG
| Entry DOI | 10.2210/pdb3lxg/pdb |
| Descriptor | cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A, 2-methoxy-6,7-dimethyl-9-propylimidazo[1,5-a]pyrido[3,2-e]pyrazine, ZINC ION, ... (5 entities in total) |
| Functional Keywords | phosphodiesterase 10a; catalytic domain, allosteric enzyme, camp, camp-binding, cgmp, cgmp-binding, hydrolase, metal-binding, nucleotide-binding |
| Biological source | Rattus norvegicus (rat) |
| Cellular location | Cytoplasm: Q9QYJ6 |
| Total number of polymer chains | 1 |
| Total formula weight | 36033.09 |
| Authors | Mosbacher, T.,Jestel, A.,Steinbacher, S. (deposition date: 2010-02-25, release date: 2010-05-19, Last modification date: 2024-02-21) |
| Primary citation | Hofgen, N.,Stange, H.,Schindler, R.,Lankau, H.J.,Grunwald, C.,Langen, B.,Egerland, U.,Tremmel, P.,Pangalos, M.N.,Marquis, K.L.,Hage, T.,Harrison, B.L.,Malamas, M.S.,Brandon, N.J.,Kronbach, T. Discovery of imidazo[1,5-a]pyrido[3,2-e]pyrazines as a new class of phosphodiesterase 10A inhibitiors. J.Med.Chem., 53:4399-4411, 2010 Cited by PubMed Abstract: Novel imidazo[1,5-a]pyrido[3,2-e]pyrazines have been synthesized and characterized as both potent and selective phosphodiesterase 10A (PDE10A) inhibitors. For in vitro characterization, inhibition of PDE10A mediated cAMP hydrolysis was used and a QSAR model was established to analyze substitution effects. The outcome of this analysis was complemented by the crystal structure of PDE10A in complex with compound 49. Qualitatively new interactions between inhibitor and binding site were found, contrasting with previously published crystal structures of papaverine-like inhibitors. In accordance with the known antipsychotic potential of PDE10A inhibitors, MK-801 induced stereotypy and hyperactivity in rats were reversed by selected compounds. Thus, a promising compound class has been identified for the treatment of schizophrenia that could circumvent side effects connected with current therapies. PubMed: 20450197DOI: 10.1021/jm1002793 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.3 Å) |
Structure validation
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