› 4zyc

X-ray diffraction
1.95Å resolution

Discovery of dihydroisoquinolinone derivatives as novel inhibitors of the p53-MDM2 interaction with a distinct binding mode: Hdm2 (MDM2) complexed with cpd5

Released:
DOI: 10.2210/pdb4zyc/pdb
PDB entry 4zyc coloured by chain, front view.
PDB entry 4zyc coloured by chain, side view.
PDB entry 4zyc coloured by chain, top view.
Source organism: Homo sapiens
Primary publication:
Discovery of dihydroisoquinolinone derivatives as novel inhibitors of the p53-MDM2 interaction with a distinct binding mode.
Gessier F, Kallen J, Jacoby E, Chène P, Stachyra-Valat T, Ruetz S, Jeay S, Holzer P, Masuya K, Furet P
Bioorg Med Chem Lett 25 3621-5 (2015)
PMID: 26141769

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: 96 amino acids
Theoretical weight: 11.17 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

2 bound ligands:
Ligand 4SS 3 x 4SS
Ligand SO4 1 x SO4
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: SLS BEAMLINE X10SA
Spacegroup: P21
Unit cell:
a: 39.02Å b: 49.78Å c: 75.287Å
α: 90° β: 92.77° γ: 90°
R-values:
R R work R free
0.222 0.22 0.259
Expression system: Escherichia coli

Quick links

Citations

14 review citations

MDM2 inhibition: an important step forward in cancer therapy.
Konopleva et al. (2020)
13 more

1 mention without citation

How To Design a Successful p53-MDM2/X Interaction Inhibitor: A Thorough Overview Based on Crystal Structures.
Estrada-Ortiz et al. (2016)