spacer
spacer

PDBsum entry 2cw0
Go to PDB code: 
protein metals Protein-protein interface(s) links
Transferase PDB id
2cw0

 

 

 

 

Loading ...

 
JSmol PyMol  
Contents
Protein chains
229 a.a. *
1119 a.a. *
1392 a.a. *
95 a.a. *
345 a.a. *
Metals
_MG ×2
_ZN ×4
* Residue conservation analysis
PDB id:
2cw0
Name: Transferase
Title: Crystal structure of thermus thermophilus RNA polymerase holoenzyme at 3.3 angstroms resolution
Structure: DNA-directed RNA polymerase alpha chain. Chain: a, b, k, l. Synonym: DNA directed RNA polymerase holoenzyme subunit alpha, rnap alpha subunit, transcriptase alpha chain, RNA polymerase alpha subunit. DNA-directed RNA polymerase beta chain. Chain: c, m. Synonym: DNA directed RNA polymerase holoenzyme subunit beta, rnap beta subunit, transcriptase beta chain, RNA polymerase beta subunit.
Source: Thermus thermophilus. Organism_taxid: 274. Organism_taxid: 300852. Strain: hb8. Organism_taxid: 262724. Strain: hb27
Biol. unit: Hexamer (from PQS)
Resolution:
3.30Å     R-factor:   0.282     R-free:   0.320
Authors: S.Tuske,S.G.Sarafianos,X.Wang,B.Hudson,E.Sineva,J.Mukhopadhyay, J.J.Birktoft,O.Leroy,S.Ismail,A.D.Clark Jr.,C.Dharia,A.Napoli, O.Laptenko,J.Lee,S.Borukhov,R.H.Ebright,E.Arnold
Key ref:
S.Tuske et al. (2005). Inhibition of bacterial RNA polymerase by streptolydigin: stabilization of a straight-bridge-helix active-center conformation. Cell, 122, 541-552. PubMed id: 16122422 DOI: 10.1016/j.cell.2005.07.017
Date:
15-Jun-05     Release date:   20-Sep-05    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
Q5SHR6  (RPOA_THET8) -  DNA-directed RNA polymerase subunit alpha from Thermus thermophilus (strain ATCC 27634 / DSM 579 / HB8)
Seq:
Struc: 		315 a.a.
229 a.a.
Protein chains
Pfam   ArchSchema ?
Q8RQE9  (RPOB_THET8) -  DNA-directed RNA polymerase subunit beta from Thermus thermophilus (strain ATCC 27634 / DSM 579 / HB8)
Seq:
Struc: 		 
Seq:
Struc: 		 
Seq:
Struc: 		1119 a.a.
1119 a.a.
Protein chains
Pfam   ArchSchema ?
Q8RQE8  (RPOC_THET8) -  DNA-directed RNA polymerase subunit beta' from Thermus thermophilus (strain ATCC 27634 / DSM 579 / HB8)
Seq:
Struc: 		 
Seq:
Struc: 		 
Seq:
Struc: 		 
Seq:
Struc: 		1524 a.a.
1392 a.a.
Protein chains
Pfam   ArchSchema ?
Q8RQE7  (RPOZ_THET8) -  DNA-directed RNA polymerase subunit omega from Thermus thermophilus (strain ATCC 27634 / DSM 579 / HB8)
Seq:
Struc: 		99 a.a.
95 a.a.*
Protein chains
Pfam   ArchSchema ?
Q5SKW1  (Q5SKW1_THET8) -  RNA polymerase sigma factor SigA from Thermus thermophilus (strain ATCC 27634 / DSM 579 / HB8)
Seq:
Struc: 		423 a.a.
345 a.a.
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 3 residue positions (black crosses)

 Enzyme reactions 
   Enzyme class: Chains A, B, C, D, E, F, K, L, M, N, O, P: E.C.2.7.7.6  - DNA-directed Rna polymerase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: RNA(n) + a ribonucleoside 5'-triphosphate = RNA(n+1) + diphosphate
RNA(n)
 + ribonucleoside 5'-triphosphate
 = RNA(n+1)
 + diphosphate
Molecule diagrams generated from .mol files obtained from the KEGG ftp site

 

 
    Added reference    
 
 
DOI no: 10.1016/j.cell.2005.07.017 Cell 122:541-552 (2005)
PubMed id: 16122422  
 
 
Inhibition of bacterial RNA polymerase by streptolydigin: stabilization of a straight-bridge-helix active-center conformation.
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, E.Arnold.
 
  ABSTRACT  
 
We define the target, mechanism, and structural basis of inhibition of bacterial RNA polymerase (RNAP) by the tetramic acid antibiotic streptolydigin (Stl). Stl binds to a site adjacent to but not overlapping the RNAP active center and stabilizes an RNAP-active-center conformational state with a straight-bridge helix. The results provide direct support for the proposals that alternative straight-bridge-helix and bent-bridge-helix RNAP-active-center conformations exist and that cycling between straight-bridge-helix and bent-bridge-helix RNAP-active-center conformations is required for RNAP function. The results set bounds on models for RNAP function and suggest strategies for design of novel antibacterial agents.
 
  Selected figure(s)  
 
Figure 1.
Figure 1. Target of Stl 		Figure 5.
Figure 5. Structural Basis of Inhibition by Stl: Stabilization of Straight-Bridge-Helix Active-Center Conformation
 
  The above figures are reprinted by permission from Cell Press: Cell (2005, 122, 541-552) copyright 2005.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21447716 S.R.Kennedy, and D.A.Erie (2011).
Templated nucleoside triphosphate binding to a noncatalytic site on RNA polymerase regulates transcription.
  Proc Natl Acad Sci U S A, 108, 6079-6084.  
20508811 G.Athanasellis, O.Igglessi-Markopoulou, and J.Markopoulos (2010).
Tetramic and tetronic acids as scaffolds in bioinorganic and bioorganic chemistry.
  Bioinorg Chem Appl, (), 315056.  
20807197 H.K.Kuo, R.Krasich, A.S.Bhagwat, and K.N.Kreuzer (2010).
Importance of the tmRNA system for cell survival when transcription is blocked by DNA-protein cross-links.
  Mol Microbiol, 78, 686-700.  
20127927 J.C.Carlson, J.L.Fortman, Y.Anzai, S.Li, D.A.Burr, and D.H.Sherman (2010).
Identification of the tirandamycin biosynthetic gene cluster from Streptomyces sp. 307-9.
  Chembiochem, 11, 564-572.  
19966797 J.Zhang, M.Palangat, and R.Landick (2010).
Role of the RNA polymerase trigger loop in catalysis and pausing.
  Nat Struct Mol Biol, 17, 99.  
20176899 M.Sánchez-Hidalgo, L.E.Núñez, C.Méndez, and J.A.Salas (2010).
Involvement of the beta subunit of RNA polymerase in resistance to streptolydigin and streptovaricin in the producer organisms Streptomyces lydicus and Streptomyces spectabilis.
  Antimicrob Agents Chemother, 54, 1684-1692.  
21124318 S.Tagami, S.Sekine, T.Kumarevel, N.Hino, Y.Murayama, S.Kamegamori, M.Yamamoto, K.Sakamoto, and S.Yokoyama (2010).
Crystal structure of bacterial RNA polymerase bound with a transcription inhibitor protein.
  Nature, 468, 978-982.
PDB codes: 3aoh 3aoi
19895816 W.J.Lane, and S.A.Darst (2010).
Molecular evolution of multisubunit RNA polymerases: structural analysis.
  J Mol Biol, 395, 686-704.  
20534498 Y.Yuzenkova, and N.Zenkin (2010).
Central role of the RNA polymerase trigger loop in intrinsic RNA hydrolysis.
  Proc Natl Acad Sci U S A, 107, 10878-10883.  
19903881 B.P.Hudson, J.Quispe, S.Lara-González, Y.Kim, H.M.Berman, E.Arnold, R.H.Ebright, and C.L.Lawson (2009).
Three-dimensional EM structure of an intact activator-dependent transcription initiation complex.
  Proc Natl Acad Sci U S A, 106, 19830-19835.
PDB code: 3iyd
19875077 C.Olano, C.Gómez, M.Pérez, M.Palomino, A.Pineda-Lucena, R.J.Carbajo, A.F.Braña, C.Méndez, and J.A.Salas (2009).
Deciphering biosynthesis of the RNA polymerase inhibitor streptolydigin and generation of glycosylated derivatives.
  Chem Biol, 16, 1031-1044.  
19439405 C.Walmacq, M.L.Kireeva, J.Irvin, Y.Nedialkov, L.Lubkowska, F.Malagon, J.N.Strathern, and M.Kashlev (2009).
Rpb9 Subunit Controls Transcription Fidelity by Delaying NTP Sequestration in RNA Polymerase II.
  J Biol Chem, 284, 19601-19612.  
19489723 E.Nudler (2009).
RNA polymerase active center: the molecular engine of transcription.
  Annu Rev Biochem, 78, 335-361.  
19481445 F.Brueckner, J.Ortiz, and P.Cramer (2009).
A movie of the RNA polymerase nucleotide addition cycle.
  Curr Opin Struct Biol, 19, 294-299.  
19883065 J.C.Carlson, S.Li, D.A.Burr, and D.H.Sherman (2009).
Isolation and characterization of tirandamycins from a marine-derived Streptomyces sp.
  J Nat Prod, 72, 2076-2079.  
19375323 J.W.Schertzer, M.L.Boulette, and M.Whiteley (2009).
More than a signal: non-signaling properties of quorum sensing molecules.
  Trends Microbiol, 17, 189-195.  
19926275 M.X.Ho, B.P.Hudson, K.Das, E.Arnold, and R.H.Ebright (2009).
Structures of RNA polymerase-antibiotic complexes.
  Curr Opin Struct Biol, 19, 715-723.  
19663400 X.Liu, and C.T.Walsh (2009).
Cyclopiazonic acid biosynthesis in Aspergillus sp.: characterization of a reductase-like R* domain in cyclopiazonate synthetase that forms and releases cyclo-acetoacetyl-L-tryptophan.
  Biochemistry, 48, 8746-8757.  
18787125 A.Feklistov, V.Mekler, Q.Jiang, L.F.Westblade, H.Irschik, R.Jansen, A.Mustaev, S.A.Darst, and R.H.Ebright (2008).
Rifamycins do not function by allosteric modulation of binding of Mg2+ to the RNA polymerase active center.
  Proc Natl Acad Sci U S A, 105, 14820-14825.  
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
19090964 C.D.Kaplan, and R.D.Kornberg (2008).
A bridge to transcription by RNA polymerase.
  J Biol, 7, 39.  
18995832 D.Bose, T.Pape, P.C.Burrows, M.Rappas, S.R.Wigneshweraraj, M.Buck, and X.Zhang (2008).
Organization of an activator-bound RNA polymerase holoenzyme.
  Mol Cell, 32, 337-346.  
18482981 D.Dutta, J.Chalissery, and R.Sen (2008).
Transcription termination factor rho prefers catalytically active elongation complexes for releasing RNA.
  J Biol Chem, 283, 20243-20251.  
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
18957204 J.Mukhopadhyay, K.Das, S.Ismail, D.Koppstein, M.Jang, B.Hudson, S.Sarafianos, S.Tuske, J.Patel, R.Jansen, H.Irschik, E.Arnold, and R.H.Ebright (2008).
The RNA polymerase "switch region" is a target for inhibitors.
  Cell, 135, 295-307.
PDB code: 3dxj
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.  
18538654 M.L.Kireeva, Y.A.Nedialkov, G.H.Cremona, Y.A.Purtov, L.Lubkowska, F.Malagon, Z.F.Burton, J.N.Strathern, and M.Kashlev (2008).
Transient reversal of RNA polymerase II active site closing controls fidelity of transcription elongation.
  Mol Cell, 30, 557-566.  
18957193 R.Sousa (2008).
Tie me up, tie me down: inhibiting RNA polymerase.
  Cell, 135, 205-207.  
18280161 S.Borukhov, and E.Nudler (2008).
RNA polymerase: the vehicle of transcription.
  Trends Microbiol, 16, 126-134.  
17145704 B.Marchand, E.P.Tchesnokov, and M.Götte (2007).
The pyrophosphate analogue foscarnet traps the pre-translocational state of HIV-1 reverse transcriptase in a Brownian ratchet model of polymerase translocation.
  J Biol Chem, 282, 3337-3346.  
17581591 D.G.Vassylyev, M.N.Vassylyeva, J.Zhang, M.Palangat, I.Artsimovitch, and R.Landick (2007).
Structural basis for substrate loading in bacterial RNA polymerase.
  Nature, 448, 163-168.
PDB codes: 2o5j 2ppb
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.  
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
16765888 J.Zlatanova, W.T.McAllister, S.Borukhov, and S.H.Leuba (2006).
Single-molecule approaches reveal the idiosyncrasies of RNA polymerases.
  Structure, 14, 953-966.  
17174884 R.Landick, and R.Kornberg (2006).
A long time in the making--the Nobel Prize for RNA polymerase.
  Cell, 127, 1087-1090.  
16900098 T.A.Steitz (2006).
Visualizing polynucleotide polymerase machines at work.
  EMBO J, 25, 3458-3468.  
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.  
16122417 S.Kyzer, J.Zhang, and R.Landick (2005).
Inhibition of RNA polymerase by streptolydigin: no cycling allowed.
  Cell, 122, 494-496.  
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 codes are shown on the right.

 

spacer
spacer