› 3edz

X-ray diffraction
1.9Å resolution

Crystal structure of catalytic domain of TACE with hydroxamate inhibitor

Released:
DOI: 10.2210/pdb3edz/pdb
PDB entry 3edz coloured by chain, front view.
PDB entry 3edz coloured by chain, side view.
PDB entry 3edz coloured by chain, top view.
Source organism: Homo sapiens
Primary publication:
Discovery of novel hydroxamates as highly potent tumor necrosis factor-alpha converting enzyme inhibitors. Part II: optimization of the S3' pocket.
Mazzola RD, Zhu Z, Sinning L, McKittrick B, Lavey B, Spitler J, Kozlowski J, Neng-Yang S, Zhou G, Guo Z, Orth P, Madison V, Sun J, Lundell D, Niu X
Bioorg Med Chem Lett 18 5809-14 (2008)
PMID: 18835710

Function and Biology Details

Reaction catalysed: 
Narrow endopeptidase specificity. Cleaves Pro-Leu-Ala-Gln-Ala-|-Val-Arg-Ser-Ser-Ser in the membrane-bound, 26-kDa form of tumor necrosis factor alpha (TNF-alpha). Similarly cleaves other membrane-anchored, cell-surface proteins to 'shed' the extracellular domains.
Biochemical function:
Biological process:
Cellular component:
  • not assigned
Sequence domains:

Structure analysis Details

Assembly composition:
monomeric (preferred)
Assembly name:
PDBe Complex ID:
PDB-CPX-160275 (preferred)
Entry contents:
1 distinct polypeptide molecule
Macromolecule:
Disintegrin and metalloproteinase domain-containing protein 17 Chains: A, B
Molecule details ›
Chains: A, B
Length: 271 amino acids
Theoretical weight: 30.67 KDa
Source organism: Homo sapiens
Expression system: Trichoplusia ni
UniProt:
  • Canonical: P78536 (Residues: 215-477; Coverage: 33%)
Gene names: ADAM17, CSVP, TACE
Sequence domains: Metallo-peptidase family M12B Reprolysin-like
Structure domains: Collagenase (Catalytic Domain)

Ligands and Environments

4 bound ligands:
Ligand ZN 2 x ZN
Ligand INN 1 x INN
Ligand CIT 2 x CIT
Ligand 550 1 x 550
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: APS BEAMLINE 17-ID
Spacegroup: P212121
Unit cell:
a: 74.796Å b: 75.702Å c: 102.877Å
α: 90° β: 90° γ: 90°
R-values:
R R work R free
0.174 0.174 0.204
Expression system: Trichoplusia ni

Quick links

Citations

2 review citations

Quinolines: a new hope against inflammation.
Mukherjee et al. (2013)
1 more

1 mention without citation

Vitamin D3 Prevents the Deleterious Effects of Testicular Torsion on Testis by Targeting miRNA-145 and ADAM17: In Silico and In Vivo Study.
Mohamed et al. (2021)