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PDBsum entry 1k83

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protein ligands metals Protein-protein interface(s) links
Transcription/toxin PDB id
1k83
Jmol
Contents
Protein chains
1366 a.a. *
1082 a.a. *
266 a.a. *
213 a.a. *
84 a.a. *
133 a.a. *
122 a.a. *
65 a.a. *
114 a.a. *
45 a.a. *
Ligands
ILX-TRX-GLY-ILE-
GLY-CSX-ASN-HYP
Metals
_MN
_ZN ×8
Waters ×69
* Residue conservation analysis
PDB id:
1k83
Name: Transcription/toxin
Title: Crystal structure of yeast RNA polymerase ii complexed with inhibitor alpha amanitin
Structure: DNA-directed RNA polymerase ii largest subunit. Chain: a. Synonym: rpb1. DNA-directed RNA polymerase ii 140kd polypeptide. Chain: b. Synonym: rpb2. DNA-directed RNA polymerase ii 45kd polypeptide. Chain: c. Synonym: rpb3.
Source: Saccharomyces cerevisiae. Baker's yeast. Organism_taxid: 4932. Strain: delta-rpb4. Amanita phalloides. Organism_taxid: 67723
Biol. unit: Undecamer (from PQS)
Resolution:
2.80Å     R-factor:   0.229     R-free:   0.280
Authors: D.A.Bushnell,P.Cramer,R.D.Kornberg
Key ref:
D.A.Bushnell et al. (2002). Structural basis of transcription: alpha-amanitin-RNA polymerase II cocrystal at 2.8 A resolution. Proc Natl Acad Sci U S A, 99, 1218-1222. PubMed id: 11805306 DOI: 10.1073/pnas.251664698
Date:
22-Oct-01     Release date:   13-Feb-02    
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.
1366 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.
1082 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.
213 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.
122 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.
45 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    
 
 
DOI no: 10.1073/pnas.251664698 Proc Natl Acad Sci U S A 99:1218-1222 (2002)
PubMed id: 11805306  
 
 
Structural basis of transcription: alpha-amanitin-RNA polymerase II cocrystal at 2.8 A resolution.
D.A.Bushnell, P.Cramer, R.D.Kornberg.
 
  ABSTRACT  
 
The structure of RNA polymerase II in a complex with the inhibitor alpha-amanitin has been determined by x-ray crystallography. The structure of the complex indicates the likely basis of inhibition and gives unexpected insight into the transcription mechanism.
 
  Selected figure(s)  
 
Figure 2.
Fig. 2. Location of -amanitin bound to pol II. (A) Cutaway view of a pol II-transcribing complex showing the location of -amanitin binding (red dot) in relation to the nucleic acids and functional elements of the enzyme. Adapted from ref. 24. (B) Ribbons representation of the pol II structure (top view in refs. 1 and 7). Eight zinc atoms are shown in light blue, the active site magnesium is magenta, the region of Rpb1 around -amanitin is light green (funnel) and dark green (bridge helix), the region of Rpb2 near -amanitin is dark blue, and -amanitin is red. This figure was prepared by using RIBBONS (25).
Figure 3.
Fig. 3. Interaction of -amanitin with pol II. (A) The chemical structure of -amanitin, with residues of pol II that lie within 4 Å [determined by using CONTACT (26)] placed near the closest contact. The C s of -amanitin are labeled with blue numbers. Hydrogen bonds are shown as dashed lines with the distances indicated. (B) Stereoview of the -amanitin binding pocket. Ball and stick models of -amanitin (red bonds) and of pol II residues within 4 Å (gray bonds) are shown. Rpb1 from A700 to A809 (funnel region) is light green. Rpb1 from A810 to A825 (bridge helix) is dark green. Rpb2 from B760 to B769 is blue. This figure was generated by using BOBSCRIPT and RASTER3D (21-23).
 
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
22173432 Y.Pommier, and C.Marchand (2012).
Interfacial inhibitors: targeting macromolecular complexes.
  Nat Rev Drug Discov, 11, 25-36.  
20207116 J.Magdalan, A.Piotrowska, A.Gomułkiewicz, T.Sozański, M.Podhorska-Okołów, A.Szeląg, and P.Dzięgiel (2011).
Benzylpenicyllin and acetylcysteine protection from α-amanitin-induced apoptosis in human hepatocyte cultures.
  Exp Toxicol Pathol, 63, 311-315.  
20829883 A.Subtil-Rodríguez, and J.C.Reyes (2010).
BRG1 helps RNA polymerase II to overcome a nucleosomal barrier during elongation, in vivo.
  EMBO Rep, 11, 751-757.  
  20509894 J.Farlow, M.A.Ichou, J.Huggins, and S.Ibrahim (2010).
Comparative whole genome sequence analysis of wild-type and cidofovir-resistant monkeypoxvirus.
  Virol J, 7, 110.  
20007273 M.Lelke, L.Brunotte, C.Busch, and S.Günther (2010).
An N-terminal region of Lassa virus L protein plays a critical role in transcription but not replication of the virus genome.
  J Virol, 84, 1934-1944.  
19895816 W.J.Lane, and S.A.Darst (2010).
Molecular evolution of multisubunit RNA polymerases: structural analysis.
  J Mol Biol, 395, 686-704.  
19078963 C.Dibner, D.Sage, M.Unser, C.Bauer, T.d'Eysmond, F.Naef, and U.Schibler (2009).
Circadian gene expression is resilient to large fluctuations in overall transcription rates.
  EMBO J, 28, 123-134.  
19489723 E.Nudler (2009).
RNA polymerase active center: the molecular engine of transcription.
  Annu Rev Biochem, 78, 335-361.  
19841728 G.Giglia-Mari, A.F.Theil, P.O.Mari, S.Mourgues, J.Nonnekens, L.O.Andrieux, J.de Wit, C.Miquel, N.Wijgers, A.Maas, M.Fousteri, J.H.Hoeijmakers, and W.Vermeulen (2009).
Differentiation driven changes in the dynamic organization of Basal transcription initiation.
  PLoS Biol, 7, e1000220.  
19389704 H.Luo, H.E.Hallen-Adams, and J.D.Walton (2009).
Processing of the phalloidin proprotein by prolyl oligopeptidase from the mushroom Conocybe albipes.
  J Biol Chem, 284, 18070-18077.  
19251626 K.F.Erhard, J.L.Stonaker, S.E.Parkinson, J.P.Lim, C.J.Hale, and J.B.Hollick (2009).
RNA polymerase IV functions in paramutation in Zea mays.
  Science, 323, 1201-1205.  
19398005 M.Kireeva, Y.A.Nedialkov, X.Q.Gong, C.Zhang, Y.Xiong, W.Moon, Z.F.Burton, and M.Kashlev (2009).
Millisecond phase kinetic analysis of elongation catalyzed by human, yeast, and Escherichia coli RNA polymerase.
  Methods, 48, 333-345.  
19855007 N.Miropolskaya, I.Artsimovitch, S.Klimasauskas, V.Nikiforov, and A.Kulbachinskiy (2009).
Allosteric control of catalysis by the F loop of RNA polymerase.
  Proc Natl Acad Sci U S A, 106, 18942-18947.  
  20046924 R.C.Todd, and S.J.Lippard (2009).
Inhibition of transcription by platinum antitumor compounds.
  Metallomics, 1, 280-291.  
19710460 Z.Liu, Z.Ma, L.S.Terada, and W.T.Garrard (2009).
Divergent roles of RelA and c-Rel in establishing chromosomal loops upon activation of the Igkappa gene.
  J Immunol, 183, 3819-3830.  
18503775 A.L.Gartel (2008).
Transcriptional inhibitors, p53 and apoptoss.
  Biochim Biophys Acta, 1786, 83-86.  
18538653 C.D.Kaplan, K.M.Larsson, and R.D.Kornberg (2008).
The RNA polymerase II trigger loop functions in substrate selection and is directly targeted by alpha-amanitin.
  Mol Cell, 30, 547-556.
PDB code: 3cqz
18552824 F.Brueckner, and P.Cramer (2008).
Structural basis of transcription inhibition by alpha-amanitin and implications for RNA polymerase II translocation.
  Nat Struct Mol Biol, 15, 811-818.
PDB code: 2vum
19056895 F.Ozsolak, L.L.Poling, Z.Wang, H.Liu, X.S.Liu, R.G.Roeder, X.Zhang, J.S.Song, and D.E.Fisher (2008).
Chromatin structure analyses identify miRNA promoters.
  Genes Dev, 22, 3172-3183.  
19055851 L.Tan, S.Wiesler, D.Trzaska, H.C.Carney, and R.O.Weinzierl (2008).
Bridge helix and trigger loop perturbations generate superactive RNA polymerases.
  J Biol, 7, 40.  
18084270 M.S.Jurica (2008).
Searching for a wrench to throw into the splicing machine.
  Nat Chem Biol, 4, 3-6.  
18573085 P.Cramer, K.J.Armache, S.Baumli, S.Benkert, F.Brueckner, C.Buchen, G.E.Damsma, S.Dengl, S.R.Geiger, A.J.Jasiak, A.Jawhari, S.Jennebach, T.Kamenski, H.Kettenberger, C.D.Kuhn, E.Lehmann, K.Leike, J.F.Sydow, and A.Vannini (2008).
Structure of eukaryotic RNA polymerases.
  Annu Rev Biophys, 37, 337-352.  
18286208 R.J.Palstra, M.Simonis, P.Klous, E.Brasset, B.Eijkelkamp, and W.de Laat (2008).
Maintenance of long-range DNA interactions after inhibition of ongoing RNA polymerase II transcription.
  PLoS ONE, 3, e1661.  
19018097 S.M.Soltis, A.E.Cohen, A.Deacon, T.Eriksson, A.González, S.McPhillips, H.Chui, P.Dunten, M.Hollenbeck, I.Mathews, M.Miller, P.Moorhead, R.P.Phizackerley, C.Smith, J.Song, H.van dem Bedem, P.Ellis, P.Kuhn, T.McPhillips, N.Sauter, K.Sharp, I.Tsyba, and G.Wolf (2008).
New paradigm for macromolecular crystallography experiments at SSRL: automated crystal screening and remote data collection.
  Acta Crystallogr D Biol Crystallogr, 64, 1210-1221.  
18378697 T.Pavelitz, A.D.Bailey, C.P.Elco, and A.M.Weiner (2008).
Human U2 snRNA genes exhibit a persistently open transcriptional state and promoter disassembly at metaphase.
  Mol Cell Biol, 28, 3573-3588.  
18679430 V.Svetlov, and E.Nudler (2008).
Jamming the ratchet of transcription.
  Nat Struct Mol Biol, 15, 777-779.  
16819507 A.Duensing, Y.Liu, N.Spardy, K.Bartoli, M.Tseng, J.A.Kwon, X.Teng, and S.Duensing (2007).
RNA polymerase II transcription is required for human papillomavirus type 16 E7- and hydroxyurea-induced centriole overduplication.
  Oncogene, 26, 215-223.  
17173017 A.Z.Ansari (2007).
Chemical crosshairs on the central dogma.
  Nat Chem Biol, 3, 2-7.  
18025465 H.E.Hallen, H.Luo, J.S.Scott-Craig, and J.D.Walton (2007).
Gene family encoding the major toxins of lethal Amanita mushrooms.
  Proc Natl Acad Sci U S A, 104, 19097-19101.  
18039033 I.Listerman, A.S.Bledau, I.Grishina, and K.M.Neugebauer (2007).
Extragenic Accumulation of RNA Polymerase II Enhances Transcription by RNA Polymerase III.
  PLoS Genet, 3, e212.  
17679091 I.Toulokhonov, J.Zhang, M.Palangat, and R.Landick (2007).
A central role of the RNA polymerase trigger loop in active-site rearrangement during transcriptional pausing.
  Mol Cell, 27, 406-419.  
17626299 J.P.May, and D.M.Perrin (2007).
Tryptathionine bridges in peptide synthesis.
  Biopolymers, 88, 714-724.  
17996703 R.Anindya, O.Aygün, and J.Q.Svejstrup (2007).
Damage-induced ubiquitylation of human RNA polymerase II by the ubiquitin ligase Nedd4, but not Cockayne syndrome proteins or BRCA1.
  Mol Cell, 28, 386-397.  
16818233 A.J.Jasiak, K.J.Armache, B.Martens, R.P.Jansen, and P.Cramer (2006).
Structural biology of RNA polymerase III: subcomplex C17/25 X-ray structure and 11 subunit enzyme model.
  Mol Cell, 23, 71-81.
PDB code: 2ckz
17212775 A.K.Rytkönen, T.Hillukkala, M.Vaara, M.Sokka, M.Jokela, R.Sormunen, H.P.Nasheuer, T.Nethanel, G.Kaufmann, H.Pospiech, and J.E.Syväoja (2006).
DNA polymerase epsilon associates with the elongating form of RNA polymerase II and nascent transcripts.
  FEBS J, 273, 5535-5549.  
16505102 C.Marchand, S.Antony, K.W.Kohn, M.Cushman, A.Ioanoviciu, B.L.Staker, A.B.Burgin, L.Stewart, and Y.Pommier (2006).
A novel norindenoisoquinoline structure reveals a common interfacial inhibitor paradigm for ternary trapping of the topoisomerase I-DNA covalent complex.
  Mol Cancer Ther, 5, 287-295.  
17129781 D.Wang, D.A.Bushnell, K.D.Westover, C.D.Kaplan, and R.D.Kornberg (2006).
Structural basis of transcription: role of the trigger loop in substrate specificity and catalysis.
  Cell, 127, 941-954.
PDB codes: 2e2h 2e2i 2e2j 2nvq 2nvs 2nvt 2nvx 2nvy 2nvz 2yu9
16461361 M.Hoshino, M.L.Qi, N.Yoshimura, T.Miyashita, K.Tagawa, Y.Wada, Y.Enokido, S.Marubuchi, P.Harjes, N.Arai, K.Oyanagi, G.Blandino, M.Sudol, T.Rich, I.Kanazawa, E.E.Wanker, M.Saitoe, and H.Okazawa (2006).
Transcriptional repression induces a slowly progressive atypical neuronal death associated with changes of YAP isoforms and p73.
  J Cell Biol, 172, 589-604.  
16765890 P.A.Meyer, P.Ye, M.Zhang, M.H.Suh, and J.Fu (2006).
Phasing RNA polymerase II using intrinsically bound Zn atoms: an updated structural model.
  Structure, 14, 973-982.
PDB code: 2b8k
16524917 V.Trinh, M.F.Langelier, J.Archambault, and B.Coulombe (2006).
Structural perspective on mutations affecting the function of multisubunit RNA polymerases.
  Microbiol Mol Biol Rev, 70, 12-36.  
15769942 C.Thiriet, and J.J.Hayes (2005).
Replication-independent core histone dynamics at transcriptionally active loci in vivo.
  Genes Dev, 19, 677-682.  
16167380 D.Temiakov, N.Zenkin, M.N.Vassylyeva, A.Perederina, T.H.Tahirov, E.Kashkina, M.Savkina, S.Zorov, V.Nikiforov, N.Igarashi, N.Matsugaki, S.Wakatsuki, K.Severinov, and D.G.Vassylyev (2005).
Structural basis of transcription inhibition by antibiotic streptolydigin.
  Mol Cell, 19, 655-666.
PDB code: 2a6h
16122422 S.Tuske, S.G.Sarafianos, X.Wang, B.Hudson, E.Sineva, J.Mukhopadhyay, J.J.Birktoft, O.Leroy, S.Ismail, A.D.Clark, C.Dharia, A.Napoli, O.Laptenko, J.Lee, S.Borukhov, R.H.Ebright, and E.Arnold (2005).
Inhibition of bacterial RNA polymerase by streptolydigin: stabilization of a straight-bridge-helix active-center conformation.
  Cell, 122, 541-552.
PDB codes: 1zyr 2cw0
15749159 Y.Pommier, and J.Cherfils (2005).
Interfacial inhibition of macromolecular interactions: nature's paradigm for drug discovery.
  Trends Pharmacol Sci, 26, 138-145.  
16094452 Z.F.Burton, M.Feig, X.Q.Gong, C.Zhang, Y.A.Nedialkov, and Y.Xiong (2005).
NTP-driven translocation and regulation of downstream template opening by multi-subunit RNA polymerases.
  Biochem Cell Biol, 83, 486-496.  
15606780 A.Kulbachinskiy, A.Feklistov, I.Krasheninnikov, A.Goldfarb, and V.Nikiforov (2004).
Aptamers to Escherichia coli core RNA polymerase that sense its interaction with rifampicin, sigma-subunit and GreB.
  Eur J Biochem, 271, 4921-4931.  
15093825 F.J.Asturias (2004).
RNA polymerase II structure, and organization of the preinitiation complex.
  Curr Opin Struct Biol, 14, 121-129.  
15200952 J.Mukhopadhyay, E.Sineva, J.Knight, R.M.Levy, and R.H.Ebright (2004).
Antibacterial peptide microcin J25 inhibits transcription by binding within and obstructing the RNA polymerase secondary channel.
  Mol Cell, 14, 739-751.  
15542830 M.Ghosh, G.Liu, G.Randall, J.Bevington, and M.Leffak (2004).
Transcription factor binding and induced transcription alter chromosomal c-myc replicator activity.
  Mol Cell Biol, 24, 10193-10207.  
15196470 P.Cramer (2004).
RNA polymerase II structure: from core to functional complexes.
  Curr Opin Genet Dev, 14, 218-226.  
15114340 S.Hahn (2004).
Structure and mechanism of the RNA polymerase II transcription machinery.
  Nat Struct Mol Biol, 11, 394-403.  
12676794 A.Shilatifard, R.C.Conaway, and J.W.Conaway (2003).
The RNA polymerase II elongation complex.
  Annu Rev Biochem, 72, 693-715.  
12672488 G.A.Hartzog (2003).
Transcription elongation by RNA polymerase II.
  Curr Opin Genet Dev, 13, 119-126.  
12914699 H.Kettenberger, K.J.Armache, and P.Cramer (2003).
Architecture of the RNA polymerase II-TFIIS complex and implications for mRNA cleavage.
  Cell, 114, 347-357.
PDB code: 1pqv
12553882 L.M.Iyer, E.V.Koonin, and L.Aravind (2003).
Evolutionary connection between the catalytic subunits of DNA-dependent RNA polymerases and eukaryotic RNA-dependent RNA polymerases and the origin of RNA polymerases.
  BMC Struct Biol, 3, 1.  
12815340 M.Machius (2003).
Structural biology: a high-tech tool for biomedical research.
  Curr Opin Nephrol Hypertens, 12, 431-438.  
12756229 T.J.Santangelo, R.A.Mooney, R.Landick, and J.W.Roberts (2003).
RNA polymerase mutations that impair conversion to a termination-resistant complex by Q antiterminator proteins.
  Genes Dev, 17, 1281-1292.  
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. Where a reference describes a PDB structure, the PDB code is shown on the right.