› 4lwv

X-ray diffraction
2.32Å resolution

The 2.3A Crystal Structure of Humanized Xenopus MDM2 with RO5545353

Released:
DOI: 10.2210/pdb4lwv/pdb
PDB entry 4lwv coloured by chain, front view.
PDB entry 4lwv coloured by chain, side view.
PDB entry 4lwv coloured by chain, top view.
Source organism: Xenopus laevis
Primary publication:
Discovery of Potent and Orally Active p53-MDM2 Inhibitors RO5353 and RO2468 for Potential Clinical Development.
Zhang Z, Chu XJ, Liu JJ, Ding Q, Zhang J, Bartkovitz D, Jiang N, Karnachi P, So SS, Tovar C, Filipovic ZM, Higgins B, Glenn K, Packman K, Vassilev L, Graves B
ACS Med Chem Lett 5 124-7 (2014)
PMID: 24900784

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, C
Molecule details ›
Chains: A, B, C
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

2 bound ligands:
Ligand 20W 3 x 20W
Ligand SO4 3 x SO4
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: APS BEAMLINE 31-ID
Spacegroup: P21212
Unit cell:
a: 88.742Å b: 132.093Å c: 35.797Å
α: 90° β: 90° γ: 90°
R-values:
R R work R free
0.233 0.23 0.284
Expression system: Escherichia coli BL21

Quick links

Citations

12 review citations

The use of spirocyclic scaffolds in drug discovery.
Zheng et al. (2014)
11 more

4 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)
3 more