5VP1

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

Functional Information from GO Data

Chain	GOid	namespace	contents
A	0004114	molecular_function	3',5'-cyclic-nucleotide phosphodiesterase activity
A	0007165	biological_process	signal transduction
A	0008081	molecular_function	phosphoric diester hydrolase activity
B	0004114	molecular_function	3',5'-cyclic-nucleotide phosphodiesterase activity
B	0007165	biological_process	signal transduction
B	0008081	molecular_function	phosphoric diester hydrolase activity
C	0004114	molecular_function	3',5'-cyclic-nucleotide phosphodiesterase activity
C	0007165	biological_process	signal transduction
C	0008081	molecular_function	phosphoric diester hydrolase activity

Functional Information from PDB Data

site_id	AC1
Number of Residues	6
Details	binding site for residue ZN A 1001

Chain	Residue
A	HIS660
A	HIS696
A	ASP697
A	ASP808
A	HOH1110
A	HOH1116

---

site_id	AC2
Number of Residues	6
Details	binding site for residue MG A 1002

Chain	Residue
A	HOH1110
A	HOH1143
A	HOH1173
A	ASP697
A	HOH1103
A	HOH1108

---

site_id	AC3
Number of Residues	5
Details	binding site for residue MG A 1003

Chain	Residue
A	GLU785
A	HOH1135
A	HOH1137
A	HOH1180
A	HOH1191

---

site_id	AC4
Number of Residues	19
Details	binding site for residue 9GA A 1004

Chain	Residue
A	THR768
A	LEU770
A	HIS773
A	THR805
A	ASP808
A	LEU809
A	GLN812
A	ILE826
A	TYR827
A	MET847
A	LEU858
A	GLN859
A	PHE862
A	ILE866
A	ILE870
A	HOH1114
A	HOH1118
A	HOH1122
A	HOH1136

---

site_id	AC5
Number of Residues	6
Details	binding site for residue ZN B 1001

Chain	Residue
B	HIS660
B	HIS696
B	ASP697
B	ASP808
B	HOH1111
B	HOH1152

---

site_id	AC6
Number of Residues	6
Details	binding site for residue MG B 1002

Chain	Residue
B	ASP697
B	HOH1102
B	HOH1111
B	HOH1120
B	HOH1124
B	HOH1163

---

site_id	AC7
Number of Residues	18
Details	binding site for residue 9GA B 1003

Chain	Residue
B	THR768
B	LEU770
B	HIS773
B	THR805
B	ASP808
B	LEU809
B	GLN812
B	TYR827
B	MET847
B	LEU858
B	GLN859
B	PHE862
B	ILE866
B	ILE870
B	HOH1113
B	HOH1126
B	HOH1134
B	HOH1155

---

site_id	AC8
Number of Residues	6
Details	binding site for residue ZN C 1001

Chain	Residue
C	HIS660
C	HIS696
C	ASP697
C	ASP808
C	HOH1103
C	HOH1144

---

site_id	AC9
Number of Residues	6
Details	binding site for residue MG C 1002

Chain	Residue
C	ASP697
C	HOH1102
C	HOH1103
C	HOH1113
C	HOH1120
C	HOH1154

---

site_id	AD1
Number of Residues	20
Details	binding site for residue 9GA C 1003

Chain	Residue
C	HIS656
C	THR768
C	LEU770
C	HIS773
C	THR805
C	ASP808
C	LEU809
C	GLN812
C	ILE826
C	TYR827
C	MET847
C	LEU858
C	GLN859
C	PHE862
C	ILE866
C	ILE870
C	HOH1112
C	HOH1129
C	HOH1130
C	HOH1146

---

Functional Information from PROSITE/UniProt

site_id	PS00126
Number of Residues	12
Details	PDEASE_I_1 3'5'-cyclic nucleotide phosphodiesterase domain signature. HDLdHrGtnNsF

Chain	Residue	Details
A	HIS696-PHE707

---

Functional Information from SwissProt/UniProt

site_id	SWS_FT_FI1
Number of Residues	3
Details	Active site: {"description":"Proton donor","evidences":[{"source":"UniProtKB","id":"O76083","evidenceCode":"ECO:0000250"}]}

Chain

Residue

Details

---

site_id	SWS_FT_FI2
Number of Residues	9
Details	Binding site: {"evidences":[{"source":"PubMed","id":"15938621","evidenceCode":"ECO:0000269"},{"source":"PubMed","id":"19828435","evidenceCode":"ECO:0000269"},{"source":"PubMed","id":"23899287","evidenceCode":"ECO:0000269"},{"source":"PDB","id":"1Z1L","evidenceCode":"ECO:0007744"},{"source":"PDB","id":"3IBJ","evidenceCode":"ECO:0007744"},{"source":"PDB","id":"3ITM","evidenceCode":"ECO:0007744"},{"source":"PDB","id":"3ITU","evidenceCode":"ECO:0007744"},{"source":"PDB","id":"4HTX","evidenceCode":"ECO:0007744"},{"source":"PDB","id":"4HTZ","evidenceCode":"ECO:0007744"},{"source":"PDB","id":"4JIB","evidenceCode":"ECO:0007744"}]}

Chain

Residue

Details

---

site_id	SWS_FT_FI3
Number of Residues	3
Details	Binding site: {"evidences":[{"source":"PubMed","id":"15938621","evidenceCode":"ECO:0000269"},{"source":"PubMed","id":"19828435","evidenceCode":"ECO:0000269"},{"source":"PubMed","id":"23899287","evidenceCode":"ECO:0000269"},{"source":"PDB","id":"1Z1L","evidenceCode":"ECO:0007744"},{"source":"PDB","id":"3ITM","evidenceCode":"ECO:0007744"},{"source":"PDB","id":"3ITU","evidenceCode":"ECO:0007744"},{"source":"PDB","id":"4HTX","evidenceCode":"ECO:0007744"},{"source":"PDB","id":"4HTZ","evidenceCode":"ECO:0007744"},{"source":"PDB","id":"4JIB","evidenceCode":"ECO:0007744"}]}

Chain

Residue

Details

---

site_id	SWS_FT_FI4
Number of Residues	324
Details	Domain: {"description":"PDEase","evidences":[{"source":"PROSITE-ProRule","id":"PRU01192","evidenceCode":"ECO:0000255"}]}

Chain

Residue

Details

---