› 4jwr

X-ray diffraction
2.35Å resolution

Co-crystal structure of MDM2 with inhibitor {(2S,5R,6S)-6-(3-chlorophenyl)-5-(4-chlorophenyl)-4-[(2S)-1-hydroxybutan-2-yl]-3-oxomorpholin-2-yl}acetic acid

Released:
DOI: 10.2210/pdb4jwr/pdb
PDB entry 4jwr coloured by chain, front view.
PDB entry 4jwr coloured by chain, side view.
PDB entry 4jwr coloured by chain, top view.
Source organism: Homo sapiens
Primary publication:
Rational design and binding mode duality of MDM2-p53 inhibitors.
Gonzalez-Lopez de Turiso F, Sun D, Rew Y, Bartberger MD, Beck HP, Canon J, Chen A, Chow D, Correll TL, Huang X, Julian LD, Kayser F, Lo MC, Long AM, McMinn D, Oliner JD, Osgood T, Powers JP, Saiki AY, Schneider S, Shaffer P, Xiao SH, Yakowec P, Yan X, Ye Q, Yu D, Zhao X, Zhou J, Medina JC, Olson SH
J Med Chem 56 4053-70 (2013)
PMID: 23597064

Function and Biology Details

Reaction catalysed: 
S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine + [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-cysteine + N(6)-ubiquitinyl-[acceptor protein]-L-lysine
Biochemical function:
  • not assigned
Biological process:
Cellular component:
Sequence domains:

Structure analysis Details

Assembly composition:
monomeric (preferred)
Assembly name:
PDBe Complex ID:
PDB-CPX-169499 (preferred)
Entry contents:
1 distinct polypeptide molecule
Macromolecule:
E3 ubiquitin-protein ligase Mdm2 Chains: A, B, C
Molecule details ›
Chains: A, B, C
Length: 95 amino acids
Theoretical weight: 11.1 KDa
Source organism: Homo sapiens
Expression system: Escherichia coli
UniProt:
  • Canonical: Q00987 (Residues: 17-111; Coverage: 19%)
Gene name: MDM2
Sequence domains: SWIB/MDM2 domain
Structure domains: SWIB/MDM2 domain

Ligands and Environments

1 bound ligand:
Ligand 1MY 3 x 1MY
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: CLSI BEAMLINE 08ID-1
Spacegroup: C2221
Unit cell:
a: 56.446Å b: 97.796Å c: 104.194Å
α: 90° β: 90° γ: 90°
R-values:
R R work R free
0.236 0.235 0.266
Expression system: Escherichia coli

Quick links

Citations

12 review citations

Drugging the p53 pathway: understanding the route to clinical efficacy.
Khoo et al. (2014)
11 more

1 mention without citation

Optimization and Evaluation of Site-Identification by Ligand Competitive Saturation (SILCS) as a Tool for Target-Based Ligand Optimization.
Ustach et al. (2019)