› 4qoc

X-ray diffraction
1.7Å resolution

crystal structure of compound 16 bound to MDM2(17-111), {(3R,5R,6S)-5-(3-CHLOROPHENYL)-6-(4-CHLOROPHENYL)-1-[(1S)-1-CYCLOPROPYL-2-(PYRROLIDIN-1-YLSULFONYL)ETHYL]-3-METHYL-2-OXOPIPERIDIN-3-YL}ACETIC ACID

Released:
DOI: 10.2210/pdb4qoc/pdb
PDB entry 4qoc coloured by chain, front view.
PDB entry 4qoc coloured by chain, side view.
PDB entry 4qoc coloured by chain, top view.
Source organism: Homo sapiens
Primary publication:
Optimization beyond AMG 232: discovery and SAR of sulfonamides on a piperidinone scaffold as potent inhibitors of the MDM2-p53 protein-protein interaction.
Wang Y, Zhu J, Liu JJ, Chen X, Mihalic J, Deignan J, Yu M, Sun D, Kayser F, McGee LR, Lo MC, Chen A, Zhou J, Ye Q, Huang X, Long AM, Yakowec P, Oliner JD, Olson SH, Medina JC
Bioorg Med Chem Lett 24 3782-5 (2014)
PMID: 25042256

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, C, E, G, I, K
Molecule details ›
Chains: A, C, E, G, I, K
Length: 96 amino acids
Theoretical weight: 11.16 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 35T 6 x 35T
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: APS BEAMLINE 21-ID-F
Spacegroup: P212121
Unit cell:
a: 56.576Å b: 98.925Å c: 103.921Å
α: 90° β: 90° γ: 90°
R-values:
R R work R free
0.238 0.238 0.253
Expression system: Escherichia coli

Quick links

Citations

2 review citations

Small-molecule MDM2/X inhibitors and PROTAC degraders for cancer therapy: advances and perspectives.
Fang et al. (2020)
1 more

1 mention without citation

Synthesis and Biological Evaluation of Novel Dispiro-Indolinones with Anticancer Activity.
Ivanenkov et al. (2023)