Structural highlights
2ovy is a 1 chain structure with sequence from Buffalo rat. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
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| Ligands: | , , , |
| Related: | 2o8h, 2ovv |
| Gene: | Pde10a, PDE10A (Buffalo rat) |
| Activity: | 3',5'-cyclic-nucleotide phosphodiesterase, with EC number 3.1.4.17 |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum |
Function
[PDE10_RAT] Plays a role in signal transduction by regulating the intracellular concentration of cyclic nucleotides. Can hydrolyze both cAMP and cGMP, but has higher affinity for cAMP and is more efficient with cAMP as substrate.[1]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
A papaverine based pharmacophore model for PDE10A inhibition was generated via SBDD and used to design a library of 4-amino-6,7-dimethoxyquinazolines. From this library emerged an aryl ether pyrrolidyl 6,7-dimethoxyquinazoline series that became the focal point for additional modeling, X-ray, and synthetic efforts toward increasing PDE10A inhibitory potency and selectivity versus PDE3A/B. These efforts culminated in the discovery of 29, a potent and selective brain penetrable inhibitor of PDE10A.
Discovery of a series of 6,7-dimethoxy-4-pyrrolidylquinazoline PDE10A inhibitors.,Chappie TA, Humphrey JM, Allen MP, Estep KG, Fox CB, Lebel LA, Liras S, Marr ES, Menniti FS, Pandit J, Schmidt CJ, Tu M, Williams RD, Yang FV J Med Chem. 2007 Jan 25;50(2):182-5. PMID:17228859[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Fujishige K, Kotera J, Omori K. Striatum- and testis-specific phosphodiesterase PDE10A isolation and characterization of a rat PDE10A. Eur J Biochem. 1999 Dec;266(3):1118-27. PMID:10583409
- ↑ Chappie TA, Humphrey JM, Allen MP, Estep KG, Fox CB, Lebel LA, Liras S, Marr ES, Menniti FS, Pandit J, Schmidt CJ, Tu M, Williams RD, Yang FV. Discovery of a series of 6,7-dimethoxy-4-pyrrolidylquinazoline PDE10A inhibitors. J Med Chem. 2007 Jan 25;50(2):182-5. PMID:17228859 doi:10.1021/jm060653b
