› 4wvs

X-ray diffraction
2.09Å resolution

Crystal structure of XIAP-BIR2 domain complexed with (S)-3-(4-methoxyphenyl)-2-((S)-2-((S)-1-((S)-2-((S)-2-(methylamino)propanamido)pent-4-ynoyl)pyrrolidine-2-carboxamido)-3-phenylpropanamido)propanoic acid

Released:
DOI: 10.2210/pdb4wvs/pdb
PDB entry 4wvs coloured by chain, front view.
PDB entry 4wvs coloured by chain, side view.
PDB entry 4wvs coloured by chain, top view.
Source organism: Homo sapiens
Primary publication:
The discovery of macrocyclic XIAP antagonists from a DNA-programmed chemistry library, and their optimization to give lead compounds with in vivo antitumor activity.
Seigal BA, Connors WH, Fraley A, Borzilleri RM, Carter PH, Emanuel SL, Fargnoli J, Kim K, Lei M, Naglich JG, Pokross ME, Posy SL, Shen H, Surti N, Talbott R, Zhang Y, Terrett NK
J Med Chem 58 2855-61 (2015)
PMID: 25695766

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:
Biological process:
Cellular component:
  • not assigned
Sequence domain:

Structure analysis Details

Assembly composition:
hetero dimer (preferred)
Assembly name:
PDBe Complex ID:
PDB-CPX-161368 (preferred)
Entry contents:
2 distinct polypeptide molecules
Macromolecules (2 distinct):
E3 ubiquitin-protein ligase XIAP Chain: A
Molecule details ›
Chain: A
Length: 98 amino acids
Theoretical weight: 11.36 KDa
Source organism: Homo sapiens
Expression system: Escherichia coli BL21(DE3)
UniProt:
  • Canonical: P98170 (Residues: 156-231; Coverage: 15%)
Gene names: API3, BIRC4, IAP3, XIAP
Sequence domains: Inhibitor of Apoptosis domain
Structure domains: Inhibitor Of Apoptosis Protein (2mihbC-IAP-1); Chain A
3,11-DIFLUORO-6,8,13-TRIMETHYL-8H-QUINO[4,3,2-KL]ACRIDIN-13-IUM Chain: B
Molecule details ›
Chain: B
Length: 5 amino acids
Theoretical weight: 676 Da
Source organism: Homo sapiens
Expression system: Not provided

Ligands and Environments

3 bound ligands:
Ligand ZN 1 x ZN
Ligand SO4 3 x SO4
Ligand GOL 1 x GOL
2 modified residues:
Ligand MAA 1 x MAA
Ligand 4LZ 1 x 4LZ

Experiments and Validation Details

Entry percentile scores
X-ray source: RIGAKU FR-E SUPERBRIGHT
Spacegroup: P21
Unit cell:
a: 28.187Å b: 39.269Å c: 32.947Å
α: 90° β: 94.53° γ: 90°
R-values:
R R work R free
0.167 0.164 0.232
Expression systems:
  • Escherichia coli BL21(DE3)
  • Not provided

Quick links

Citations

13 review citations

DNA-encoded chemistry: enabling the deeper sampling of chemical space.
Goodnow et al. (2017)
12 more

1 mention without citation

Regulation of XIAP Turnover Reveals a Role for USP11 in Promotion of Tumorigenesis.
Zhou et al. (2017)