› 4jrg

X-ray diffraction
1.9Å resolution

The 1.9A crystal structure of humanized Xenopus MDM2 with RO5313109 - a pyrrolidine MDM2 inhibitor

Released:
DOI: 10.2210/pdb4jrg/pdb
PDB entry 4jrg coloured by chain, front view.
PDB entry 4jrg coloured by chain, side view.
PDB entry 4jrg coloured by chain, top view.
Source organism: Xenopus laevis
Primary publication:
Discovery of RG7388, a potent and selective p53-MDM2 inhibitor in clinical development.
Ding Q, Zhang Z, Liu JJ, Jiang N, Zhang J, Ross TM, Chu XJ, Bartkovitz D, Podlaski F, Janson C, Tovar C, Filipovic ZM, Higgins B, Glenn K, Packman K, Vassilev LT, Graves B
J Med Chem 56 5979-83 (2013)
PMID: 23808545

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-157449 (preferred)
Entry contents:
1 distinct polypeptide molecule
Macromolecule:
E3 ubiquitin-protein ligase Mdm2 Chains: A, B
Molecule details ›
Chains: A, B
Length: 85 amino acids
Theoretical weight: 9.83 KDa
Source organism: Xenopus laevis
Expression system: Escherichia coli BL21
UniProt:
  • Canonical: P56273 (Residues: 21-105; Coverage: 18%)
Gene name: mdm2
Sequence domains: SWIB/MDM2 domain
Structure domains: SWIB/MDM2 domain

Ligands and Environments

1 bound ligand:
Ligand I09 2 x I09
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: RIGAKU MICROMAX-007
Spacegroup: C2
Unit cell:
a: 73.542Å b: 72.796Å c: 43.865Å
α: 90° β: 111.78° γ: 90°
R-values:
R R work R free
0.252 0.25 0.288
Expression system: Escherichia coli BL21

Quick links

Citations

114 review citations

Targeting apoptosis in cancer therapy.
Carneiro et al. (2020)
113 more

11 mentions without citation

Small-molecule inhibitors of the MDM2-p53 protein-protein interaction (MDM2 Inhibitors) in clinical trials for cancer treatment.
Zhao et al. (2015)
10 more