› 2wo8

X-ray diffraction
2Å resolution

MMP12 complex with a beta hydroxy carboxylic acid

Released:
DOI: 10.2210/pdb2wo8/pdb
PDB entry 2wo8 coloured by chain, front view.
PDB entry 2wo8 coloured by chain, side view.
PDB entry 2wo8 coloured by chain, top view.
Source organism: Homo sapiens
Primary publication:
The identification of beta-hydroxy carboxylic acids as selective MMP-12 inhibitors.
Holmes IP, Gaines S, Watson SP, Lorthioir O, Walker A, Baddeley SJ, Herbert S, Egan D, Convery MA, Singh OM, Gross JW, Strelow JM, Smith RH, Amour AJ, Brown D, Martin SL
Bioorg Med Chem Lett 19 5760-3 (2009)
PMID: 19703773

Function and Biology Details

Reaction catalysed: 
Hydrolysis of soluble and insoluble elastin (1). Specific cleavages are also produced at -Ala(14)-|-Leu- and -Tyr(16)-|-Leu- in the B chain of insulin (2).
Biochemical function:
Biological process:
Cellular component:
Sequence domains:

Structure analysis Details

Assembly composition:
monomeric (preferred)
Assembly name:
PDBe Complex ID:
PDB-CPX-153971 (preferred)
Entry contents:
1 distinct polypeptide molecule
Macromolecule:
Macrophage metalloelastase Chains: A, B, C, D
Molecule details ›
Chains: A, B, C, D
Length: 164 amino acids
Theoretical weight: 18.23 KDa
Source organism: Homo sapiens
Expression system: Escherichia coli
UniProt:
  • Canonical: P39900 (Residues: 106-268; Coverage: 36%)
Gene names: HME, MMP12
Sequence domains: Matrixin
Structure domains: Collagenase (Catalytic Domain)

Ligands and Environments

6 bound ligands:
Ligand ZN 8 x ZN
Ligand CA 6 x CA
Ligand 077 2 x 077
Ligand SO4 5 x SO4
Ligand 023 2 x 023
Ligand GOL 2 x GOL
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: SRS BEAMLINE PX14.2
Spacegroup: P1
Unit cell:
a: 46.043Å b: 65.264Å c: 67.808Å
α: 66.47° β: 83.86° γ: 71.37°
R-values:
R R work R free
0.187 0.184 0.246
Expression system: Escherichia coli

Quick links

Citations

5 citation in other articles

Discovery of a New Class of Potent MMP Inhibitors by Structure-Based Optimization of the Arylsulfonamide Scaffold.
Mori et al. (2013)
4 more

1 mention without citation

Simple pseudo-dipeptides with a P2' glutamate: a novel inhibitor family of matrix metalloproteases and other metzincins.
Devel et al. (2012)