› 6iwi

X-ray diffraction
2.16Å resolution

Crystal structure of PDE5A in complex with a novel inhibitor

Released:
DOI: 10.2210/pdb6iwi/pdb
Model geometry
Fit model/data
PDB entry 6iwi coloured by chain, front view.
PDB entry 6iwi coloured by chain, side view.
PDB entry 6iwi coloured by chain, top view.
Source organism: Homo sapiens
Primary publication:
Pharmacokinetics-Driven Optimization of 4(3 H)-Pyrimidinones as Phosphodiesterase Type 5 Inhibitors Leading to TPN171, a Clinical Candidate for the Treatment of Pulmonary Arterial Hypertension.
Wang Z, Jiang X, Zhang X, Tian G, Yang R, Wu J, Zou X, Liu Z, Yang X, Wu C, Shi J, Li J, Suo J, Wang Y, Zhang R, Xu Z, Gong X, He Y, Zhu W, Aisa HA, Jiang H, Xu Y, Shen J
J Med Chem 62 4979-4990 (2019)
PMID: 31021628

Function and Biology Details

Reaction catalysed: 
Guanosine 3',5'-cyclic phosphate + H(2)O = guanosine 5'-phosphate
Biochemical function:
Biological process:
Cellular component:
  • not assigned
Sequence domains:

Structure analysis Details

Assembly composition:
monomeric (preferred)
Assembly name:
PDBe Complex ID:
PDB-CPX-131208 (preferred)
Entry contents:
1 distinct polypeptide molecule
Macromolecule:
cGMP-specific 3',5'-cyclic phosphodiesterase Chain: A
Molecule details ›
Chain: A
Length: 347 amino acids
Theoretical weight: 40.09 KDa
Source organism: Homo sapiens
Expression system: Escherichia coli BL21(DE3)
UniProt:
  • Canonical: O76074 (Residues: 535-860; Coverage: 37%)
Gene names: PDE5, PDE5A
Sequence domains: 3'5'-cyclic nucleotide phosphodiesterase

Ligands and Environments

3 bound ligands:
Ligand MG 1 x MG
Ligand ZN 1 x ZN
Ligand B0C 1 x B0C
No modified residues

Experiments and Validation Details

wwPDB Validation report is not available for this entry.
X-ray source: SSRF BEAMLINE BL18U1
Spacegroup: P3121
Unit cell:
a: 74.748Å b: 74.748Å c: 132.02Å
α: 90° β: 90° γ: 120°
R-values:
R R work R free
0.187 0.185 0.226
Expression system: Escherichia coli BL21(DE3)

Quick links

Citations

3 review citations

Therapy for Pulmonary Arterial Hypertension: Glance on Nitric Oxide Pathway.
Tettey et al. (2021)
2 more