› 4lwu

X-ray diffraction
1.14Å resolution

The 1.14A Crystal Structure of Humanized Xenopus MDM2 with RO5499252

Released:
DOI: 10.2210/pdb4lwu/pdb
PDB entry 4lwu coloured by chain, front view.
PDB entry 4lwu coloured by chain, side view.
PDB entry 4lwu coloured by chain, top view.
Source organism: Xenopus laevis
Primary publication:
Discovery of potent and selective spiroindolinone MDM2 inhibitor, RO8994, for cancer therapy.
Zhang Z, Ding Q, Liu JJ, Zhang J, Jiang N, Chu XJ, Bartkovitz D, Luk KC, Janson C, Tovar C, Filipovic ZM, Higgins B, Glenn K, Packman K, Vassilev LT, Graves B
Bioorg Med Chem 22 4001-9 (2014)
PMID: 24997575

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 Chain: A
Molecule details ›
Chain: A
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 20U 1 x 20U
Ligand SO4 1 x SO4
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: SLS BEAMLINE X10SA
Spacegroup: P21212
Unit cell:
a: 40.554Å b: 78.341Å c: 24.703Å
α: 90° β: 90° γ: 90°
R-values:
R R work R free
0.216 0.215 0.226
Expression system: Escherichia coli BL21

Quick links

Citations

9 review citations

Targeting transcription factors in cancer - from undruggable to reality.
Bushweller JH. (2019)
8 more

1 mention without citation

Discovery of spirooxindole-derived small-molecule compounds as novel HDAC/MDM2 dual inhibitors and investigation of their anticancer activity.
Zhao et al. (2022)