› 6thp

X-ray diffraction
2.54Å resolution

Neprilysin in complex with the inhibitor (R)-4-(1-carboxy-3-(3'-chlorobiphenyl-4-yl)propan-2-ylamino)-4-oxobutanoic acid

Released:
DOI: 10.2210/pdb6thp/pdb
PDB entry 6thp coloured by chain, front view.
PDB entry 6thp coloured by chain, side view.
PDB entry 6thp coloured by chain, top view.
Source organism: Homo sapiens
Primary publication:
Structure-Guided Design of Substituted Biphenyl Butanoic Acid Derivatives as Neprilysin Inhibitors.
Kawanami T, Karki RG, Cody E, Liu Q, Liang G, Ksander GM, Rigel DF, Schiering N, Gong Y, Coppola GM, Iwaki Y, Sun R, Neubert A, Fan L, Ingles S, D'Arcy A, Villard F, Ramage P, Jeng AY, Leung-Chu J, Liu J, Beil M, Fu F, Chen W, Cumin F, Wiesmann C, Mogi M
ACS Med Chem Lett 11 188-194 (2020)
PMID: 32071687

Function and Biology Details

Reaction catalysed: 
Preferential cleavage of polypeptides between hydrophobic residues, particularly with Phe or Tyr at P1'.
Biochemical function:
Biological process:
Cellular component:
Sequence domains:

Structure analysis Details

Assembly composition:
monomeric (preferred)
Assembly name:
PDBe Complex ID:
PDB-CPX-140129 (preferred)
Entry contents:
1 distinct polypeptide molecule
Macromolecule:
Neprilysin Chains: A, B
Molecule details ›
Chains: A, B
Length: 696 amino acids
Theoretical weight: 79.53 KDa
Source organism: Homo sapiens
UniProt:
  • Canonical: P08473 (Residues: 55-750; Coverage: 93%)
Gene names: EPN, MME
Sequence domains:

Ligands and Environments

3 bound ligands:
Ligand NAG 8 x NAG
Ligand ZN 2 x ZN
Ligand N9Q 2 x N9Q
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: SLS BEAMLINE X10SA
Spacegroup: P212121
Unit cell:
a: 59.79Å b: 109.39Å c: 248.018Å
α: 90° β: 90° γ: 90°
R-values:
R R work R free
0.208 0.205 0.264

Quick links

Citations

3 citation in other articles

Structural analysis of Mycobacterium tuberculosis M13 metalloprotease Zmp1 open states.
Liang et al. (2021)
2 more

1 mention without citation

New Borane-Protected Derivatives of α-Aminophosphonous Acid as Anti-Osteosarcoma Agents: ADME Analysis and Molecular Modeling, In Vitro Studies on Anti-Cancer Activities, and NEP Inhibition as a Possible Mechanism of Anti-Proliferative Activity.
Mizerska-Kowalska et al. (2022)