› 2viq

X-ray diffraction
2Å resolution

Fragment-Based Discovery of Mexiletine Derivatives as Orally Bioavailable Inhibitors of Urokinase-Type Plasminogen Activator

Released:
DOI: 10.2210/pdb2viq/pdb
PDB entry 2viq coloured by chain, front view.
PDB entry 2viq coloured by chain, side view.
PDB entry 2viq coloured by chain, top view.
Source organism: Homo sapiens
Primary publication:
Fragment-based discovery of mexiletine derivatives as orally bioavailable inhibitors of urokinase-type plasminogen activator.
Frederickson M, Callaghan O, Chessari G, Congreve M, Cowan SR, Matthews JE, McMenamin R, Smith DM, Vinković M, Wallis NG
J Med Chem 51 183-6 (2008)
PMID: 18163548

Function and Biology Details

Reaction catalysed: 
Specific cleavage of Arg-|-Val bond in plasminogen to form plasmin.
Biochemical function:
Biological process:
Cellular component:
  • not assigned
Sequence domains:
Structure domain:

Structure analysis Details

Assembly composition:
monomeric (preferred)
Assembly name:
PDBe Complex ID:
PDB-CPX-133249 (preferred)
Entry contents:
1 distinct polypeptide molecule
Macromolecule:
Urokinase-type plasminogen activator chain B Chain: A
Molecule details ›
Chain: A
Length: 253 amino acids
Theoretical weight: 28.44 KDa
Source organism: Homo sapiens
Expression system: Escherichia coli
UniProt:
  • Canonical: P00749 (Residues: 179-431; Coverage: 62%)
Gene name: PLAU
Sequence domains: Trypsin
Structure domains: Trypsin-like serine proteases

Ligands and Environments

2 bound ligands:
Ligand ACT 1 x ACT
Ligand D55 1 x D55
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: RIGAKU RUH3R
Spacegroup: P212121
Unit cell:
a: 52.176Å b: 53.949Å c: 81.756Å
α: 90° β: 90° γ: 90°
R-values:
R R work R free
0.184 0.18 0.264
Expression system: Escherichia coli

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Citations

9 review citations

Structural biology in fragment-based drug design.
Murray et al. (2010)
8 more