Research workbench
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
Analyse Discovery of clinical candidate N-{(1S)-1-[3-fluoro-4… in the GL1X research workbench: secondary structure, accessibility, pockets, interfaces, conservation, variants, modifications, peptides, crosslinks and neighbours on the 3D structure.
- PDB
- 5VP1
- Type
- protein
- Length
- 993 residues
- Chains
- 3
- Method
- x-ray diffraction
- Collection
- MolNFT v1 / PDB
- Contract
- 0xDE3723766Bc32dcACD03C17BaA400A7B36837Eba
- Owner
- 0x3396CDB397284571d12822B4ae1189a8E22AAAAA
- Molecule
- Cgmp-dependent 3',5'-cyclic phosphodiesterase
- EC
- 3.1.4.17
- UniProt
- O00408
- Ligands
- 9GA, MG, ZN
- Pockets
- 7 · best druggability 0.78
Structure
x-ray diffraction · 3 distinct chains · 69% helix, 0% strand (DSSP).
| Chain | Molecule | Type | Residues | Secondary structure | UniProt |
|---|---|---|---|---|---|
| A | Cgmp-dependent 3',5'-cyclic phosphodiesterase (EC 3.1.4.17) | protein | 338 | 70% helix, 0% strand | O00408 |
| B | Cgmp-dependent 3',5'-cyclic phosphodiesterase (EC 3.1.4.17) | protein | 342 | 69% helix, 0% strand | O00408 |
| C | Cgmp-dependent 3',5'-cyclic phosphodiesterase (EC 3.1.4.17) | protein | 313 | 68% helix, 0% strand | O00408 |
Ligands and binding sites
- 9GA · N-{(1S)-2-hydroxy-2-methyl-1-[4-(trifluoromethoxy) phenyl]propyl}-6-methyl-5-(3-methyl-1H-1,2,4-triazol-1-yl)pyrazolo[1,5-a]pyrimidine-3-carboxamide · ligand · 3 copies · chains A, B, C
- MG · Magnesium ion · metal · 4 copies · chains A, B, C
- ZN · Zinc ion · metal · 3 copies · chains A, B, C
Binding sites are the residues within 4.5 Å of a ligand's heavy atoms.
Pockets
7 pockets found on a 1 Å grid, 4 with a druggability of 0.5 or more.
| Volume (ų) | Druggability | Buriedness | Lining residues | Inside | |
|---|---|---|---|---|---|
| 1 | 449 | 0.78 | 0.86 | 40 | MG, 9GA |
| 2 | 765 | 0.77 | 0.81 | 93 | empty |
| 3 | 438 | 0.77 | 0.85 | 43 | MG, 9GA |
| 4 | 433 | 0.76 | 0.85 | 42 | MG, 9GA |
| 5 | 64 | 0.41 | 0.81 | 18 | empty |
Interfaces
3 interfaces between chains.
- A–B · 967 Ų buried · 8 hydrogen bonds · protein-protein
- B–C · 297 Ų buried · 3 hydrogen bonds · protein-protein
- A–C · 69 Ų buried · 0 hydrogen bonds · protein-protein
Compared structures
- 5VP1 · Discovery of Clinical Candidate N-{(1S)-1-[3-Fluoro-4-(trifluoromethoxy)phenyl]-2-methoxye… · the same entry in another collection · chain A against A, TM-score 1.00
Analyse
- Open in the research workbench: secondary structure, accessibility, pockets, interfaces, conservation, variants, modifications, peptides and crosslinks on the 3D structure
- Every structure of UniProt O00408
- Elsewhere: RCSB PDB 5VP1 · PDBe 5VP1 · UniProt O00408
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