› 5lav

X-ray diffraction
1.73Å resolution

Novel Spiro[3H-indole-3,2 -pyrrolidin]-2(1H)-one Inhibitors of the MDM2-p53 Interaction: HDM2 (MDM2) in complex with compound 6b

Released:
DOI: 10.2210/pdb5lav/pdb
PDB entry 5lav coloured by chain, front view.
PDB entry 5lav coloured by chain, side view.
PDB entry 5lav coloured by chain, top view.
Source organism: Homo sapiens
Primary publication:
Discovery of Novel Spiro[3H-indole-3,2'-pyrrolidin]-2(1H)-one Compounds as Chemically Stable and Orally Active Inhibitors of the MDM2-p53 Interaction.
Gollner A, Rudolph D, Arnhof H, Bauer M, Blake SM, Boehmelt G, Cockroft XL, Dahmann G, Ettmayer P, Gerstberger T, Karolyi-Oezguer J, Kessler D, Kofink C, Ramharter J, Rinnenthal J, Savchenko A, Schnitzer R, Weinstabl H, Weyer-Czernilofsky U, Wunberg T, McConnell DB
J Med Chem 59 10147-10162 (2016)
PMID: 27775892

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 Chain: A
Molecule details ›
Chain: A
Length: 93 amino acids
Theoretical weight: 10.88 KDa
Source organism: Homo sapiens
Expression system: Escherichia coli BL21(DE3)
UniProt:
  • Canonical: Q00987 (Residues: 19-111; Coverage: 19%)
Gene name: MDM2
Sequence domains: SWIB/MDM2 domain
Structure domains: SWIB/MDM2 domain

Ligands and Environments

2 bound ligands:
Ligand 6SK 1 x 6SK
Ligand SO4 1 x SO4
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: SLS BEAMLINE X06SA
Spacegroup: P6122
Unit cell:
a: 56.651Å b: 56.651Å c: 104.085Å
α: 90° β: 90° γ: 120°
R-values:
R R work R free
0.244 0.242 0.273
Expression system: Escherichia coli BL21(DE3)

Quick links

Citations

7 review citations

Decoding the messaging of the ubiquitin system using chemical and protein probes.
Henneberg et al. (2021)
6 more

1 mention without citation

Absolute Binding Free Energy Calculations for Highly Flexible Protein MDM2 and Its Inhibitors.
Singh et al. (2020)