› 4k69

X-ray diffraction
1.5Å resolution

Crystal Structure of Human Chymase in Complex with Fragment Linked Benzimidazolone Inhibitor: (3S)-3-{3-[(6-bromo-2-oxo-2,3-dihydro-1H-indol-4-yl)methyl]-2-oxo-2,3-dihydro-1H-benzimidazol-1-yl}hexanoic acid

Released:
DOI: 10.2210/pdb4k69/pdb
PDB entry 4k69 coloured by chain, front view.
PDB entry 4k69 coloured by chain, side view.
PDB entry 4k69 coloured by chain, top view.
Source organism: Homo sapiens
Primary publication:
Discovery of potent, selective chymase inhibitors via fragment linking strategies.
Taylor SJ, Padyana AK, Abeywardane A, Liang S, Hao MH, De Lombaert S, Proudfoot J, Farmer BS, Li X, Collins B, Martin L, Albaugh DR, Hill-Drzewi M, Pullen SS, Takahashi H
J Med Chem 56 4465-81 (2013)
PMID: 23659209

Function and Biology Details

Reaction catalysed: 
Preferential cleavage: Phe-|- > Tyr-|- > Trp-|- > Leu-|-.
Biochemical function:
Biological process:
Cellular component:
Sequence domains:

Structure analysis Details

Assembly composition:
monomeric (preferred)
Assembly name:
PDBe Complex ID:
PDB-CPX-150125 (preferred)
Entry contents:
1 distinct polypeptide molecule
Macromolecule:
Chymase Chain: A
Molecule details ›
Chain: A
Length: 226 amino acids
Theoretical weight: 24.99 KDa
Source organism: Homo sapiens
Expression system: Spodoptera frugiperda
UniProt:
  • Canonical: P23946 (Residues: 22-247; Coverage: 99%)
Gene names: CMA1, CYH, CYM
Sequence domains: Trypsin
Structure domains: Trypsin-like serine proteases

Ligands and Environments

3 bound ligands:
Ligand ZN 2 x ZN
Ligand NAG 1 x NAG
Ligand 1P9 1 x 1P9
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: RIGAKU FR-E SUPERBRIGHT
Spacegroup: P43
Unit cell:
a: 74.365Å b: 74.365Å c: 49.474Å
α: 90° β: 90° γ: 90°
R-values:
R R work R free
0.198 0.197 0.223
Expression system: Spodoptera frugiperda

Quick links

Citations

3 review citations

Twenty years on: the impact of fragments on drug discovery.
Erlanson et al. (2016)
2 more