5TZC
Crystal Structure of human PDE2a in complex with (5S)-1-[(3-bromo-4-fluorophenyl)carbonyl]-3,3-difluoro-5-{5-methyl-[1,2,4]triazolo[1,5-a]pyrimidin-7-yl}piperidine
Summary for 5TZC
| Entry DOI | 10.2210/pdb5tzc/pdb |
| Related | 5TZ3 5TZA 5TZH 5TZW 5TZX 5TZZ 5U00 |
| Descriptor | cGMP-dependent 3',5'-cyclic phosphodiesterase, (3-bromo-4-fluorophenyl)[(5S)-3,3-difluoro-5-(5-methyl[1,2,4]triazolo[1,5-a]pyrimidin-7-yl)piperidin-1-yl]methanone, ZINC ION, ... (5 entities in total) |
| Functional Keywords | phosphodiesterase, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor |
| Biological source | Homo sapiens (Human) |
| Cellular location | Isoform PDE2A3: Cell membrane ; Lipid-anchor . Isoform PDE2A2: Mitochondrion matrix . Isoform PDE2A1: Cytoplasm . Isoform 5: Mitochondrion : O00408 |
| Total number of polymer chains | 4 |
| Total formula weight | 162848.04 |
| Authors | Xu, R.,Aertgeerts, K. (deposition date: 2016-11-21, release date: 2017-02-22, Last modification date: 2024-03-06) |
| Primary citation | Gomez, L.,Massari, M.E.,Vickers, T.,Freestone, G.,Vernier, W.,Ly, K.,Xu, R.,McCarrick, M.,Marrone, T.,Metz, M.,Yan, Y.G.,Yoder, Z.W.,Lemus, R.,Broadbent, N.J.,Barido, R.,Warren, N.,Schmelzer, K.,Neul, D.,Lee, D.,Andersen, C.B.,Sebring, K.,Aertgeerts, K.,Zhou, X.,Tabatabaei, A.,Peters, M.,Breitenbucher, J.G. Design and Synthesis of Novel and Selective Phosphodiesterase 2 (PDE2a) Inhibitors for the Treatment of Memory Disorders. J. Med. Chem., 60:2037-2051, 2017 Cited by PubMed Abstract: A series of potent and selective [1,2,4]triazolo[1,5-a]pyrimidine PDE2a inhibitors is reported. The design and improvement of the binding properties of this series was achieved using X-ray crystal structures in conjunction with careful analysis of electronic and structural requirements for the PDE2a enzyme. One of the lead compounds, compound 27 (DNS-8254), was identified as a potent and highly selective PDE2a enzyme inhibitor with favorable rat pharmacokinetic properties. Interestingly, the increased potency of compound 27 was facilitated by the formation of a halogen bond with the oxygen of Tyr827 present in the PDE2a active site. In vivo, compound 27 demonstrated significant memory enhancing effects in a rat model of novel object recognition. Taken together, these data suggest that compound 27 may be a useful tool to explore the pharmacology of selective PDE2a inhibition. PubMed: 28165743DOI: 10.1021/acs.jmedchem.6b01793 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.36 Å) |
Structure validation
Download full validation report
