3M4O

RNA polymerase II elongation complex B


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 3.57 Å
  • R-Value Free: 0.292 
  • R-Value Work: 0.241 
  • R-Value Observed: 0.244 

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This is version 1.2 of the entry. See complete history


Literature

X-ray structure and mechanism of RNA polymerase II stalled at an antineoplastic monofunctional platinum-DNA adduct.

Wang, D.Zhu, G.Huang, X.Lippard, S.J.

(2010) Proc Natl Acad Sci U S A 107: 9584-9589

  • DOI: https://doi.org/10.1073/pnas.1002565107
  • Primary Citation of Related Structures:  
    3M3Y, 3M4O

  • PubMed Abstract: 

    DNA is a major target of anticancer drugs. The resulting adducts interfere with key cellular processes, such as transcription, to trigger downstream events responsible for drug activity. cis-Diammine(pyridine)chloroplatinum(II), cDPCP or pyriplatin, is a monofunctional platinum(II) analogue of the widely used anticancer drug cisplatin having significant anticancer properties with a different spectrum of activity. Its novel structure-activity properties hold promise for overcoming drug resistance and improving the spectrum of treatable cancers over those responsive to cisplatin. However, the detailed molecular mechanism by which cells process DNA modified by pyriplatin and related monofunctional complexes is not at all understood. Here we report the structure of a transcribing RNA polymerase II (pol II) complex stalled at a site-specific monofunctional pyriplatin-DNA adduct in the active site. The results reveal a molecular mechanism of pol II transcription inhibition and drug action that is dramatically different from transcription inhibition by cisplatin and UV-induced 1,2-intrastrand cross-links. Our findings provide insight into structure-activity relationships that may apply to the entire family of monofunctional DNA-damaging agents and pave the way for rational improvement of monofunctional platinum anticancer drugs.


  • Organizational Affiliation

    Department of Structural Biology, Stanford University School of Medicine, Stanford, CA 94305, USA. dongwang@ucsd.edu


Macromolecules

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Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
DNA-directed RNA polymerase II subunit RPB11,733Saccharomyces cerevisiaeMutation(s): 0 
EC: 2.7.7.6
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Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
DNA-directed RNA polymerase II subunit RPB21,224Saccharomyces cerevisiaeMutation(s): 0 
EC: 2.7.7.6
UniProt
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Entity ID: 3
MoleculeChains Sequence LengthOrganismDetailsImage
DNA-directed RNA polymerase II subunit RPB3318Saccharomyces cerevisiaeMutation(s): 0 
UniProt
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Entity ID: 4
MoleculeChains Sequence LengthOrganismDetailsImage
DNA-directed RNA polymerases I, II, and III subunit RPABC1D [auth E]215Saccharomyces cerevisiaeMutation(s): 0 
UniProt
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UniProt GroupP20434
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Entity ID: 5
MoleculeChains Sequence LengthOrganismDetailsImage
DNA-directed RNA polymerases I, II, and III subunit RPABC2E [auth F]155Saccharomyces cerevisiaeMutation(s): 0 
UniProt
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Entity ID: 6
MoleculeChains Sequence LengthOrganismDetailsImage
DNA-directed RNA polymerases I, II, and III subunit RPABC3F [auth H]146Saccharomyces cerevisiaeMutation(s): 0 
UniProt
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Entity ID: 7
MoleculeChains Sequence LengthOrganismDetailsImage
DNA-directed RNA polymerase II subunit RPB9G [auth I]122Saccharomyces cerevisiaeMutation(s): 0 
UniProt
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Entity ID: 8
MoleculeChains Sequence LengthOrganismDetailsImage
DNA-directed RNA polymerases I, II, and III subunit RPABC5H [auth J]70Saccharomyces cerevisiaeMutation(s): 0 
UniProt
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Entity ID: 9
MoleculeChains Sequence LengthOrganismDetailsImage
DNA-directed RNA polymerase II subunit RPB11I [auth K]120Saccharomyces cerevisiaeMutation(s): 0 
UniProt
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Entity ID: 10
MoleculeChains Sequence LengthOrganismDetailsImage
DNA-directed RNA polymerases I, II, and III subunit RPABC4J [auth L]70Saccharomyces cerevisiaeMutation(s): 0 
UniProt
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Entity ID: 11
MoleculeChains LengthOrganismImage
RNA (5'-R(*AP*UP*GP*GP*AP*GP*AP*GP*GP*A)-3')K [auth R]10N/A
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Entity ID: 12
MoleculeChains LengthOrganismImage
DNA (28-MER)L [auth T]28N/A
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Entity ID: 13
MoleculeChains LengthOrganismImage
DNA (5'-D(P*GP*TP*GP*GP*TP*TP*AP*TP*GP*GP*GP*TP*AP*G)-3')M [auth N]14N/A
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Small Molecules
Ligands 3 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
C7P
Query on C7P

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W [auth T]cis-diammine(pyridine)chloroplatinum(II)
C5 H11 Cl N3 Pt
JFCCPKJRZXSLGC-UHFFFAOYSA-M
ZN
Query on ZN

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N [auth A]
O [auth A]
Q [auth B]
R [auth C]
S [auth I]
N [auth A],
O [auth A],
Q [auth B],
R [auth C],
S [auth I],
T [auth I],
U [auth J],
V [auth L]
ZINC ION
Zn
PTFCDOFLOPIGGS-UHFFFAOYSA-N
MG
Query on MG

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P [auth A]MAGNESIUM ION
Mg
JLVVSXFLKOJNIY-UHFFFAOYSA-N
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 3.57 Å
  • R-Value Free: 0.292 
  • R-Value Work: 0.241 
  • R-Value Observed: 0.244 
  • Space Group: C 1 2 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 168.114α = 90
b = 222.131β = 100.99
c = 191.782γ = 90
Software Package:
Software NamePurpose
HKL-2000data collection
MLPHAREphasing
REFMACrefinement
DENZOdata reduction
HKL-2000data scaling

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2010-05-12
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance
  • Version 1.2: 2023-09-06
    Changes: Data collection, Database references, Derived calculations, Refinement description