Brand  (β version)

PDB ID: 5VP0

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Ligands
Code Name Style Show Link
ZN Zinc ion PoSSuM
MG Magnesium ion PoSSuM
9GJ N-{(1s)-1-[3-fluoro-4-(trifluoromethoxy)phenyl]-2-methoxyethyl}-7-methoxy-2-oxo-2,3-dihydropyrido[2,3-B]pyrazine-4(1h)-carboxamide PoSSuM
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Structure summary

Code : 5VP0   PDBj   RCSB PDB   PDBe
Header : HYDROLASE/HYDROLASE INHIBITOR
Title : Discovery of Clinical Candidate N-{(1S)-1-[3-Fluoro-4-(trifluoromethoxy)phenyl]-2-methoxyethyl}-7-methoxy-2-oxo-2,3-dihydropyrido[2,3-B]pyrazine-4(1H)-carboxamide (TAK-915), A Highly Potent, Selective, and Brain-Penetrating Phosphodiesterase 2A Inhibitor for the Treatment of Cognitive Disorders
Release Data : 2017-08-23
Compound :
mol_id molecule chains synonym
1 cGMP-dependent 3',5'-cyclic phosphodiesterase A,B,C Cyclic GMP-stimulated phosphodiesterase,cGSPDE
ec: 3.1.4.17
fragment: UNP residues 322-663
Source :
mol_id organism_scientific organism_common expression_system
1 Homo sapiens  (taxid:9606) Human Baculovirus expression vector pFastBac1-HM  (taxid:274590)
gene: PDE2A
expression_system_strain: Sf9
Authors : Hoffman, I.D.
Keywords : Inhibitor, Phosphodiesterase, Brain-Pentrating, Cognitive Disorders, HYDROLASE-HYDROLASE INHIBITOR complex
Exp. method : X-RAY DIFFRACTION ( 2.2000 Å )
Citation :

Discovery of Clinical Candidate N-((1S)-1-(3-Fluoro-4-(trifluoromethoxy)phenyl)-2-methoxyethyl)-7-methoxy-2-oxo-2,3-dihydropyrido[2,3-b]pyrazine-4(1H)-carboxamide (TAK-915): A Highly Potent, Selective, and Brain-Penetrating Phosphodiesterase 2A Inhibitor for the Treatment of Cognitive Disorders.

Mikami, S.,Nakamura, S.,Ashizawa, T.  et al.
(2017)  J. Med. Chem.  60 : 7677 - 7702

PubMed: 28796496
DOI: 10.1021/acs.jmedchem.7b00807

Reaction

Chain : A, B, C
UniProt : O00408 (PDE2A_HUMAN)
Reaction: EC: Evidence:
Physiological Direction:
a nucleoside 3',5'-cyclic phosphate + H2O = a nucleoside 5'- phosphate + H(+) 3.1.4.17 PubMed:15938621, PubMed:29392776, PubMed:9210593
left-to-right PubMed:9210593
3',5'-cyclic GMP + H2O = GMP + H(+) - PubMed:15938621, PubMed:29392776, PubMed:9210593
left-to-right PubMed:9210593
3',5'-cyclic AMP + H2O = AMP + H(+) - PubMed:15938621, PubMed:29392776, PubMed:9210593
left-to-right PubMed:9210593
Cofactor: Evidence: Note:
Zn(2+) ECO:0000269 | PubMed:15938621
ECO:0000269 | PubMed:19828435
ECO:0000269 | PubMed:23899287
Binds 2 divalent metal cations per subunit. Site 1 may preferentially bind zinc ions.
Mg(2+) ECO:0000269 | PubMed:15938621
ECO:0000269 | PubMed:19828435
ECO:0000269 | PubMed:23899287
Binds 2 divalent metal cations per subunit. Site 2 has a preference for magnesium ions.