4WVU

CRYSTAL STRUCTURE OF XIAP-BIR2 DOMAIN COMPLEXED WITH LIGAND BOUND

Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.02 Å
  • R-Value Free: 0.178 
  • R-Value Work: 0.139 
  • R-Value Observed: 0.141 

wwPDB Validation   3D Report Full Report


This is version 2.0 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 XIAP98Homo sapiensMutation(s): 2 
Gene Names: XIAP, API3, BIRC4, IAP3
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
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  • 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-IUM5N/AMutation(s): 0 
Sequence Annotations
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  • Reference Sequence
Small Molecules
Modified Residues  2 Unique
IDChains TypeFormula2D DiagramParent
HOX
Query on HOX
B
L-PEPTIDE LINKINGC9 H12 N2 O2PHE
MAA
Query on MAA
B
L-PEPTIDE LINKINGC4 H9 N O2ALA
Biologically Interesting Molecules (External Reference) 1 Unique
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.02 Å
  • R-Value Free: 0.178 
  • R-Value Work: 0.139 
  • R-Value Observed: 0.141 
  • Space Group: P 1 21 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 28.261α = 90
b = 39.328β = 95.51
c = 33.058γ = 90
Software Package:
Software NamePurpose
XDSdata reduction
SCALAdata scaling
BUSTERrefinement
PHASERphasing

Structure Validation

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View more in-depth experimental data
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
  • Version 2.0: 2023-11-15
    Changes: Atomic model, Data collection, Database references, Derived calculations, Other, Source and taxonomy