5IFO

X-ray structure of HSA-Myr-KP1019


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 3.20 Å
  • R-Value Free: 0.262 
  • R-Value Work: 0.244 
  • R-Value Observed: 0.245 

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Ligand Structure Quality Assessment 


This is version 1.5 of the entry. See complete history


Literature

X-ray Structure Analysis of Indazolium trans-[Tetrachlorobis(1H-indazole)ruthenate(III)] (KP1019) Bound to Human Serum Albumin Reveals Two Ruthenium Binding Sites and Provides Insights into the Drug Binding Mechanism.

Bijelic, A.Theiner, S.Keppler, B.K.Rompel, A.

(2016) J Med Chem 59: 5894-5903

  • DOI: https://doi.org/10.1021/acs.jmedchem.6b00600
  • Primary Citation of Related Structures:  
    5IFO

  • PubMed Abstract: 

    Ruthenium(III) complexes are promising candidates for anticancer drugs, especially the clinically studied indazolium trans-[tetrachlorobis(1H-indazole)ruthenate(III)] (KP1019) and its analogue sodium trans-[tetrachlorobis(1H-indazole)ruthenate(III)] (NKP-1339). Several studies have emphasized the likely role of human serum proteins in the transportation and accumulation of ruthenium(III) complexes in tumors. Therefore, the interaction between KP1019 and human serum albumin was investigated by means of X-ray crystallography and inductively coupled plasma mass spectrometry (ICP-MS). The structural data unambiguously reveal the binding of two ruthenium atoms to histidine residues 146 and 242, which are both located within well-known hydrophobic binding pockets of albumin. The ruthenium centers are octahedrally coordinated by solvent molecules revealing the dissociation of both indazole ligands from the ruthenium-based drug. However, a binding mechanism is proposed indicating the importance of the indazole ligands for binding site recognition and thus their indispensable role for the binding of KP1019.


  • Organizational Affiliation

    Fakultät für Chemie, Institut für Biophysikalische Chemie, Universität Wien , Althanstraße 14, 1090 Wien, Austria.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Serum albumin585Homo sapiensMutation(s): 0 
UniProt & NIH Common Fund Data Resources
Find proteins for P02768 (Homo sapiens)
Explore P02768 
Go to UniProtKB:  P02768
PHAROS:  P02768
GTEx:  ENSG00000163631 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP02768
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 3.20 Å
  • R-Value Free: 0.262 
  • R-Value Work: 0.244 
  • R-Value Observed: 0.245 
  • Space Group: C 1 2 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 181.11α = 90
b = 38.06β = 105.06
c = 94.95γ = 90
Software Package:
Software NamePurpose
PHENIXrefinement
XDSdata scaling
PHENIXphasing
XDSdata reduction

Structure Validation

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Ligand Structure Quality Assessment 


Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
Austrian Science FundAustriaP23711

Revision History  (Full details and data files)

  • Version 1.0: 2016-06-01
    Type: Initial release
  • Version 1.1: 2016-07-06
    Changes: Database references
  • Version 1.2: 2017-09-06
    Changes: Author supporting evidence
  • Version 1.3: 2018-01-31
    Changes: Database references
  • Version 1.4: 2019-10-16
    Changes: Data collection
  • Version 1.5: 2024-01-10
    Changes: Data collection, Database references, Derived calculations, Refinement description