› 5vk0

X-ray diffraction
1.8Å resolution

Crystal structure of human MDM2 in complex with a 12-mer lysine-cysteine side chain dithiocarbamate stapled peptide inhibitor PMI

Released:
DOI: 10.2210/pdb5vk0/pdb
PDB entry 5vk0 coloured by chain, front view.
PDB entry 5vk0 coloured by chain, side view.
PDB entry 5vk0 coloured by chain, top view.
Source organisms:
Primary publication:
Dithiocarbamate-inspired side chain stapling chemistry for peptide drug design.
Li X, Tolbert WD, Hu HG, Gohain N, Zou Y, Niu F, He WX, Yuan W, Su JC, Pazgier M, Lu W
Chem Sci 10 1522-1530 (2019)
PMID: 30809370

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:
hetero dimer (preferred)
Assembly name:
PDBe Complex ID:
PDB-CPX-166219 (preferred)
Entry contents:
2 distinct polypeptide molecules
Macromolecules (2 distinct):
E3 ubiquitin-protein ligase Mdm2 Chains: A, C, E, G, I, K, M, O, Q, S, U, W
Molecule details ›
Chains: A, C, E, G, I, K, M, O, Q, S, U, W
Length: 85 amino acids
Theoretical weight: 10.04 KDa
Source organism: Homo sapiens
Expression system: Not provided
UniProt:
  • Canonical: Q00987 (Residues: 25-109; Coverage: 17%)
Gene name: MDM2
Sequence domains: SWIB/MDM2 domain
Structure domains: SWIB/MDM2 domain
Lysine-cysteine side chain dithiocarbamate stapled peptide inhibitor PMI Chains: B, D, F, H, J, L, N, P, R, T, V, X
Molecule details ›
Chains: B, D, F, H, J, L, N, P, R, T, V, X
Length: 14 amino acids
Theoretical weight: 1.52 KDa
Source organism: synthetic construct
Expression system: Not provided

Ligands and Environments

1 bound ligand:
Ligand CL 2 x CL
1 modified residue:
Ligand 9E7 12 x 9E7

Experiments and Validation Details

Entry percentile scores
X-ray source: SSRL BEAMLINE BL12-2
Spacegroup: C2221
Unit cell:
a: 90.838Å b: 157.47Å c: 196.65Å
α: 90° β: 90° γ: 90°
R-values:
R R work R free
0.2 0.198 0.247
Expression system: Not provided

Quick links

Citations

3 review citations

PROTACs: great opportunities for academia and industry (an update from 2020 to 2021).
He et al. (2022)
2 more

2 mentions without citation

Stapled Peptides Inhibitors: A New Window for Target Drug Discovery.
Ali et al. (2019)
1 more