› 7q24

X-ray diffraction
2Å resolution

Crystal structure of Angiotensin-1 converting enzyme N-domain in complex with dual ACE/NEP inhibitor AD011

Released:
DOI: 10.2210/pdb7q24/pdb
PDB entry 7q24 coloured by chain, front view.
PDB entry 7q24 coloured by chain, side view.
PDB entry 7q24 coloured by chain, top view.
Source organism: Homo sapiens
Primary publication:
Probing the Requirements for Dual Angiotensin-Converting Enzyme C-Domain Selective/Neprilysin Inhibition.
Arendse LB, Cozier GE, Eyermann CJ, Basarab GS, Schwager SL, Chibale K, Acharya KR, Sturrock ED
J Med Chem 65 3371-3387 (2022)
PMID: 35113565

Function and Biology Details

Reaction catalysed: 
Release of a C-terminal dipeptide, oligopeptide-|-Xaa-Yaa, when Xaa is not Pro, and Yaa is neither Asp nor Glu. Thus, conversion of angiotensin I to angiotensin II, with increase in vasoconstrictor activity, but no action on angiotensin II.
Biochemical function:
Biological process:
Cellular component:
Sequence domain:

Structure analysis Details

Assembly composition:
monomeric (preferred)
Assembly name:
PDBe Complex ID:
PDB-CPX-146325 (preferred)
Entry contents:
1 distinct polypeptide molecule
Macromolecules (4 distinct):
Angiotensin-converting enzyme, soluble form Chains: A, B
Molecule details ›
Chains: A, B
Length: 629 amino acids
Theoretical weight: 72.61 KDa
Source organism: Homo sapiens
Expression system: Cricetulus griseus
UniProt:
  • Canonical: P12821 (Residues: 30-657; Coverage: 49%)
Gene names: ACE, DCP, DCP1
Sequence domains: Angiotensin-converting enzyme

Ligands and Environments

Carbohydrate polymer : NEW Components: NAG
Carbohydrate polymer
Carbohydrate polymer : NEW Components: NAG, BMA, FUC
Carbohydrate polymer
Carbohydrate polymer : NEW Components: NAG, FUC
Carbohydrate polymer
11 bound ligands:
Ligand PEG 4 x PEG
Ligand P33 1 x P33
Ligand ACT 3 x ACT
Ligand EDO 4 x EDO
Ligand P6G 1 x P6G
Ligand ZN 2 x ZN
Ligand CL 2 x CL
Ligand MG 2 x MG
Ligand 8KC 2 x 8KC
Ligand PG4 2 x PG4
Ligand NAG 1 x NAG
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: DIAMOND BEAMLINE I04-1
Spacegroup: P1
Unit cell:
a: 72.766Å b: 77.608Å c: 81.647Å
α: 88.931° β: 64.553° γ: 75.009°
R-values:
R R work R free
0.186 0.185 0.214
Expression system: Cricetulus griseus

Quick links

Citations

2 citation in other articles

Structural basis for the inhibition of human angiotensin-1 converting enzyme by fosinoprilat.
Cozier et al. (2022)
1 more

3 mentions without citation

Small molecule angiotensin converting enzyme inhibitors: A medicinal chemistry perspective.
Zheng et al. (2022)
2 more