› 7q28

X-ray diffraction
1.65Å resolution

Crystal structure of Angiotensin-1 converting enzyme C-domain in complex with dual ACE/NEP inhibitor AD012

Released:
DOI: 10.2210/pdb7q28/pdb
PDB entry 7q28 coloured by chain, front view.
PDB entry 7q28 coloured by chain, side view.
PDB entry 7q28 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 (2 distinct):
Angiotensin-converting enzyme, soluble form Chain: A
Molecule details ›
Chain: A
Length: 597 amino acids
Theoretical weight: 68.86 KDa
Source organism: Homo sapiens
Expression system: Cricetulus griseus
UniProt:
  • Canonical: P12821 (Residues: 642-1238; Coverage: 47%)
Gene names: ACE, DCP, DCP1
Sequence domains: Angiotensin-converting enzyme

Ligands and Environments

Carbohydrate polymer : NEW Components: NAG, BMA, MAN, FUC
Carbohydrate polymer
7 bound ligands:
Ligand NAG 1 x NAG
Ligand BO3 3 x BO3
Ligand 8J9 1 x 8J9
Ligand PEG 1 x PEG
Ligand EDO 2 x EDO
Ligand ZN 1 x ZN
Ligand CL 2 x CL
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: DIAMOND BEAMLINE I03
Spacegroup: P212121
Unit cell:
a: 56.254Å b: 84.78Å c: 133.376Å
α: 90° β: 90° γ: 90°
R-values:
R R work R free
0.164 0.163 0.183
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

2 mentions without citation

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