spacer
spacer

PDBsum entry 3m3y

Go to PDB code: 
protein dna_rna ligands metals Protein-protein interface(s) links
Transferase/DNA-RNA hybrid PDB id
3m3y
Jmol
Contents
Protein chains
1395 a.a. *
1106 a.a. *
266 a.a. *
214 a.a. *
84 a.a. *
133 a.a. *
119 a.a. *
65 a.a. *
114 a.a. *
46 a.a. *
DNA/RNA
Ligands
C7P
Metals
_ZN ×8
_MG
* Residue conservation analysis
PDB id:
3m3y
Name: Transferase/DNA-RNA hybrid
Title: RNA polymerase ii elongation complex c
Structure: DNA-directed RNA polymerase ii subunit rpb1. Chain: a. Synonym: RNA polymerase ii subunit b1, RNA polymerase ii su DNA-directed RNA polymerase iii largest subunit, RNA polyme subunit b220. DNA-directed RNA polymerase ii subunit rpb2. Chain: b. Synonym: RNA polymerase ii subunit 2, DNA-directed RNA poly 140 kda polypeptide, b150.
Source: Saccharomyces cerevisiae. Brewer's yeast,lager beer yeast,yeast. Organism_taxid: 4932. Synthetic: yes. Synthetic: yes
Resolution:
3.18Å     R-factor:   0.209     R-free:   0.255
Authors: D.Wang,G.Zhu,X.Huang,S.J.Lippard
Key ref: D.Wang et al. (2010). X-ray structure and mechanism of RNA polymerase II stalled at an antineoplastic monofunctional platinum-DNA adduct. Proc Natl Acad Sci U S A, 107, 9584-9589. PubMed id: 20448203
Date:
10-Mar-10     Release date:   12-May-10    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P04050  (RPB1_YEAST) -  DNA-directed RNA polymerase II subunit RPB1
Seq:
Struc:
 
Seq:
Struc:
 
Seq:
Struc:
 
Seq:
Struc:
1733 a.a.
1395 a.a.
Protein chain
Pfam   ArchSchema ?
P08518  (RPB2_YEAST) -  DNA-directed RNA polymerase II subunit RPB2
Seq:
Struc:
 
Seq:
Struc:
 
Seq:
Struc:
1224 a.a.
1106 a.a.
Protein chain
Pfam   ArchSchema ?
P16370  (RPB3_YEAST) -  DNA-directed RNA polymerase II subunit RPB3
Seq:
Struc:
318 a.a.
266 a.a.
Protein chain
Pfam   ArchSchema ?
P20434  (RPAB1_YEAST) -  DNA-directed RNA polymerases I, II, and III subunit RPABC1
Seq:
Struc:
215 a.a.
214 a.a.
Protein chain
Pfam   ArchSchema ?
P20435  (RPAB2_YEAST) -  DNA-directed RNA polymerases I, II, and III subunit RPABC2
Seq:
Struc:
155 a.a.
84 a.a.
Protein chain
Pfam   ArchSchema ?
P20436  (RPAB3_YEAST) -  DNA-directed RNA polymerases I, II, and III subunit RPABC3
Seq:
Struc:
146 a.a.
133 a.a.
Protein chain
Pfam   ArchSchema ?
P27999  (RPB9_YEAST) -  DNA-directed RNA polymerase II subunit RPB9
Seq:
Struc:
122 a.a.
119 a.a.
Protein chain
Pfam   ArchSchema ?
P22139  (RPAB5_YEAST) -  DNA-directed RNA polymerases I, II, and III subunit RPABC5
Seq:
Struc:
70 a.a.
65 a.a.
Protein chain
Pfam   ArchSchema ?
P38902  (RPB11_YEAST) -  DNA-directed RNA polymerase II subunit RPB11
Seq:
Struc:
120 a.a.
114 a.a.
Protein chain
Pfam   ArchSchema ?
P40422  (RPAB4_YEAST) -  DNA-directed RNA polymerases I, II, and III subunit RPABC4
Seq:
Struc:
70 a.a.
46 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: Chains A, B: E.C.2.7.7.6  - DNA-directed Rna polymerase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: Nucleoside triphosphate + RNA(n) = diphosphate + RNA(n+1)
Nucleoside triphosphate
+ RNA(n)
= diphosphate
+ RNA(n+1)
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     cytoplasm   7 terms 
  Biological process     transcription, RNA-dependent   14 terms 
  Biochemical function     RNA polymerase II activity     14 terms  

 

 
    reference    
 
 
Proc Natl Acad Sci U S A 107:9584-9589 (2010)
PubMed id: 20448203  
 
 
X-ray structure and mechanism of RNA polymerase II stalled at an antineoplastic monofunctional platinum-DNA adduct.
D.Wang, G.Zhu, X.Huang, S.J.Lippard.
 
  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.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
21251871 H.Burger, W.J.Loos, K.Eechoute, J.Verweij, R.H.Mathijssen, and E.A.Wiemer (2011).
Drug transporters of platinum-based anticancer agents and their clinical significance.
  Drug Resist Updat, 14, 22-34.  
  21452186 N.Graf, W.H.Ang, G.Zhu, M.Myint, and S.J.Lippard (2011).
Role of endonucleases XPF and XPG in nucleotide excision repair of platinated DNA and cisplatin/oxaliplatin cytotoxicity.
  Chembiochem, 12, 1115-1123.  
20730221 G.Ma, Y.Min, F.Huang, T.Jiang, and Y.Liu (2010).
Thioether binding mediates monofunctional platinum antitumor reagents to trans configuration in DNA interactions.
  Chem Commun (Camb), 46, 6938-6940.  
  20677309 N.J.Farrer, J.A.Woods, L.Salassa, Y.Zhao, K.S.Robinson, G.Clarkson, F.S.Mackay, and P.J.Sadler (2010).
A potent trans-diimine platinum anticancer complex photoactivated by visible light.
  Angew Chem Int Ed Engl, 49, 8905-8908.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time.