4WVT

Crystal structure of XIAP-BIR2 domain complexed with ligand bound


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.96 Å
  • R-Value Free: 0.230 
  • R-Value Work: 0.174 
  • R-Value Observed: 0.177 

wwPDB Validation   3D Report Full Report


This is version 1.1 of the entry. See complete history


Literature

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, B.A.Connors, W.H.Fraley, A.Borzilleri, R.M.Carter, P.H.Emanuel, S.L.Fargnoli, J.Kim, K.Lei, M.Naglich, J.G.Pokross, M.E.Posy, S.L.Shen, H.Surti, N.Talbott, R.Zhang, Y.Terrett, N.K.

(2015) J Med Chem 58: 2855-2861

  • DOI: https://doi.org/10.1021/jm501892g
  • Primary Citation of Related Structures:  
    4WVS, 4WVT, 4WVU

  • PubMed Abstract: 

    Affinity selection screening of macrocycle libraries derived from DNA-programmed chemistry identified XIAP BIR2 and BIR3 domain inhibitors that displace bound pro-apoptotic caspases. X-ray cocrystal structures of key compounds with XIAP BIR2 suggested potency-enhancing structural modifications. Optimization of dimeric macrocycles with similar affinity for both domains were potent pro-apoptotic agents in cancer cell lines and efficacious in shrinking tumors in a mouse xenograft model.


  • Organizational Affiliation

    †Ensemble Therapeutics Corp, 99 Erie Street, Cambridge, Massachusetts 02139, United States.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
E3 ubiquitin-protein ligase XIAP
A, B
98Homo sapiensMutation(s): 2 
Gene Names: XIAPAPI3BIRC4IAP3
EC: 6.3.2
UniProt & NIH Common Fund Data Resources
Find proteins for P98170 (Homo sapiens)
Explore P98170 
Go to UniProtKB:  P98170
PHAROS:  P98170
GTEx:  ENSG00000101966 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP98170
Sequence Annotations
Expand
  • Reference Sequence

Find similar proteins by:  Sequence   |   3D Structure  

Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
3,11-DIFLUORO-6,8,13-TRIMETHYL-8H-QUINO[4,3,2-KL]ACRIDIN-13-IUM
C, D
6N/AMutation(s): 0 
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Modified Residues  1 Unique
IDChains TypeFormula2D DiagramParent
MAA
Query on MAA
C, D
L-PEPTIDE LINKINGC4 H9 N O2ALA
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.96 Å
  • R-Value Free: 0.230 
  • R-Value Work: 0.174 
  • R-Value Observed: 0.177 
  • Space Group: P 1 21 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 33.2α = 90
b = 38.53β = 89.83
c = 56.77γ = 90
Software Package:
Software NamePurpose
HKL-2000data reduction
HKL-2000data scaling
BUSTERrefinement
PHASERphasing
HKLdata reduction
SCALEPACKdata scaling

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2015-03-04
    Type: Initial release
  • Version 1.1: 2015-04-08
    Changes: Database references