1AIO

CRYSTAL STRUCTURE OF A DOUBLE-STRANDED DNA CONTAINING THE MAJOR ADDUCT OF THE ANTICANCER DRUG CISPLATIN


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.60 Å
  • R-Value Free: 0.251 
  • R-Value Work: 0.206 
  • R-Value Observed: 0.206 

wwPDB Validation   3D Report Full Report


This is version 1.3 of the entry. See complete history


Literature

Crystal structure of double-stranded DNA containing the major adduct of the anticancer drug cisplatin.

Takahara, P.M.Rosenzweig, A.C.Frederick, C.A.Lippard, S.J.

(1995) Nature 377: 649-652

  • DOI: https://doi.org/10.1038/377649a0
  • Primary Citation of Related Structures:  
    1AIO

  • PubMed Abstract: 

    The success of cisplatin in cancer chemotherapy derives from its ability to crosslink DNA and alter the structure. Most cisplatin-DNA adducts are intrastrand d(GpG) and d(ApG) crosslinks, which unwind and bend the duplex to facilitate the binding of proteins that contain one or more high-mobility group (HMG) domains. When HMG-domain proteins such as HMG1, IXR (intrastrand-crosslink recognition) protein from yeast, or human upstream-binding factor (hUBF) bind cisplatin intrastrand crosslinks, they can be diverted from their natural binding sites on the genome and shield the adducts from excision repair. These activities sensitize cells to cisplatin and contribute to its cytotoxic properties. Crystallographic information about the structure of cisplatin-DNA adducts has been limited to short single-stranded deoxyoligonucleotides such as cis-[Pt(NH3)2(d(pGpG))]. Here we describe the X-ray structure at 2.6 A resolution of a double-stranded DNA dodecamer containing this adduct. Our information provides, to our knowledge, the first crystallographic look at a platinated DNA duplex and should help the design of new platinum and other metal crosslinking antitumour drug candidates. Moreover, the structure reveals a unique fusion of A- and B-type DNA segments that could be of more general importance.


  • Organizational Affiliation

    Department of Chemistry, Massachusetts Institute of Technology, Cambridge 02139, USA.


Macromolecules

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Entity ID: 1
MoleculeChains LengthOrganismImage
DNA (5'-D(*CP*CP*(BRU)P*CP*TP*[PT(NH3)2(GP*GP)]*TP*CP*TP*CP*C)-3')
A, C
12N/A
Sequence Annotations
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  • Reference Sequence

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Entity ID: 2
MoleculeChains LengthOrganismImage
DNA (5'-D(*GP*GP*AP*GP*AP*CP*CP*AP*GP*AP*GP*G)-3')
B, D
12N/A
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
CPT
Query on CPT

Download Ideal Coordinates CCD File 
E [auth A],
F [auth C]
Cisplatin
Cl2 H6 N2 Pt
LXZZYRPGZAFOLE-UHFFFAOYSA-L
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.60 Å
  • R-Value Free: 0.251 
  • R-Value Work: 0.206 
  • R-Value Observed: 0.206 
  • Space Group: P 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 31.27α = 79.81
b = 35.46β = 84.75
c = 47.01γ = 82.79
Software Package:
Software NamePurpose
X-PLORrefinement
DENZOdata reduction
SCALEPACKdata scaling

Structure Validation

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Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 1997-04-24
    Type: Initial release
  • Version 1.1: 2008-05-22
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Non-polymer description, Version format compliance
  • Version 1.3: 2024-02-07
    Changes: Data collection, Database references, Derived calculations