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PDBsum entry 1ynj
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protein ligands metals Protein-protein interface(s) links
Transferase PDB id
1ynj

 

 

 

 

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Contents
Protein chains
230 a.a. *
1114 a.a. *
1238 a.a. *
249 a.a. *
95 a.a. *
Ligands
SRN
Metals
_ZN ×2
* Residue conservation analysis
PDB id:
1ynj
Name: Transferase
Title: Taq RNA polymerase-sorangicin complex
Structure: DNA-directed RNA polymerase alpha chain. Chain: a, b. Synonym: rnap alpha subunit, transcriptase alpha chain, RNA polymerase alpha subunit. DNA-directed RNA polymerase beta chain. Chain: c. Synonym: rnap beta subunit, transcriptase beta chain, RNA polymerase beta subunit. DNA-directed RNA polymerase beta' chain.
Source: Thermus aquaticus. Organism_taxid: 271. Organism_taxid: 271
Biol. unit: Dodecamer (from PQS)
Resolution:
3.20Å     R-factor:   0.284     R-free:   0.346
Authors: E.A.Campbell,O.Pavlova,N.Zenkin,F.Leon,H.Irschik,R.Jansen, K.Severinov,S.A.Darst
Key ref:
E.A.Campbell et al. (2005). Structural, functional, and genetic analysis of sorangicin inhibition of bacterial RNA polymerase. EMBO J, 24, 674-682. PubMed id: 15692574 DOI: 10.1038/sj.emboj.7600499
Date:
24-Jan-05     Release date:   15-Mar-05    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
Q9KWU8  (RPOA_THEAQ) -  DNA-directed RNA polymerase subunit alpha from Thermus aquaticus
Seq:
Struc: 		314 a.a.
230 a.a.
Protein chain
Pfam   ArchSchema ?
Q9KWU7  (RPOB_THEAQ) -  DNA-directed RNA polymerase subunit beta from Thermus aquaticus
Seq:
Struc: 		 
Seq:
Struc: 		 
Seq:
Struc: 		1119 a.a.
1114 a.a.
Protein chain
Pfam   ArchSchema ?
Q9KWU6  (RPOC_THEAQ) -  DNA-directed RNA polymerase subunit beta' from Thermus aquaticus
Seq:
Struc: 		 
Seq:
Struc: 		 
Seq:
Struc: 		 
Seq:
Struc: 		1524 a.a.
1238 a.a.
Protein chain
Pfam   ArchSchema ?
Q9KWU6  (RPOC_THEAQ) -  DNA-directed RNA polymerase subunit beta' from Thermus aquaticus
Seq:
Struc: 		 
Seq:
Struc: 		 
Seq:
Struc: 		 
Seq:
Struc: 		1524 a.a.
249 a.a.
Protein chain
Pfam   ArchSchema ?
Q9EVV4  (RPOZ_THEAQ) -  DNA-directed RNA polymerase subunit omega from Thermus aquaticus
Seq:
Struc: 		99 a.a.
95 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: Chains A, B, C, D, J, K: 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: 10.1038/sj.emboj.7600499 EMBO J 24:674-682 (2005)
PubMed id: 15692574  
 
 
Structural, functional, and genetic analysis of sorangicin inhibition of bacterial RNA polymerase.
E.A.Campbell, O.Pavlova, N.Zenkin, F.Leon, H.Irschik, R.Jansen, K.Severinov, S.A.Darst.
 
  ABSTRACT  
 
A combined structural, functional, and genetic approach was used to investigate inhibition of bacterial RNA polymerase (RNAP) by sorangicin (Sor), a macrolide polyether antibiotic. Sor lacks chemical and structural similarity to the ansamycin rifampicin (Rif), an RNAP inhibitor widely used to treat tuberculosis. Nevertheless, structural analysis revealed Sor binds in the same RNAP beta subunit pocket as Rif, with almost complete overlap of RNAP binding determinants, and functional analysis revealed that both antibiotics inhibit transcription by directly blocking the path of the elongating transcript at a length of 2-3 nucleotides. Genetic analysis indicates that Rif binding is extremely sensitive to mutations expected to change the shape of the antibiotic binding pocket, while Sor is not. We suggest that conformational flexibility of Sor, in contrast to the rigid conformation of Rif, allows Sor to adapt to changes in the binding pocket. This has important implications for drug design against rapidly mutating targets.
 
  Selected figure(s)  
 
Figure 1.
Figure 1 Chemical formulas for RNAP inhibitors Sor (top) and Rif (bottom). For clarity, only selected atoms discussed in the text are numbered. 		Figure 4.
Figure 4 Rif and Sor interactions with RNAP, and conformational flexibility. (A, B) Schematic drawing of RNAP subunit interactions with Rif (A) and Sor (B), modified from LIGPLOT (Wallace et al, 1995). Residues forming van der Waal's interactions are indicated; those participating in hydrogen bonds are shown in a ball-and-stick representation, with hydrogen bonds depicted as lines. (C -E) Results of molecular dynamics simulations. Starting conformations of Rif (C) or Sor (D, E) are shown as thick bonds and colored light orange (Rif) or light green (Sor). The final conformations after 10 independent molecular dynamics simulations are shown as thinner bonds and darker color. In (E), only atoms C22 -C30/O5 -O6 were allowed to move during the simulation. In all of the images, flexible, branched segments of each antibiotic that do not interact with RNAP (C38 -C43/N2 -N4 for Rif, C36 -C45/O10 -O11 for Sor) were included in the simulations, but were not included in the alignment and are not shown.
 
  The above figures are reprinted from an Open Access publication published by Macmillan Publishers Ltd: EMBO J (2005, 24, 674-682) copyright 2005.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20715267 H.Irschik, M.Kopp, K.J.Weissman, K.Buntin, J.Piel, and R.Müller (2010).
Analysis of the sorangicin gene cluster reinforces the utility of a combined phylogenetic/retrobiosynthetic analysis for deciphering natural product assembly by trans-AT PKS.
  Chembiochem, 11, 1840-1849.  
20520915 K.J.Weissman, and R.Müller (2010).
Myxobacterial secondary metabolites: bioactivities and modes-of-action.
  Nat Prod Rep, 27, 1276-1295.  
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.  
20829291 S.Patrick, G.W.Blakely, S.Houston, J.Moore, V.R.Abratt, M.Bertalan, A.M.Cerdeño-Tárraga, M.A.Quail, N.Corton, C.Corton, A.Bignell, A.Barron, L.Clark, S.D.Bentley, and J.Parkhill (2010).
Twenty-eight divergent polysaccharide loci specifying within- and amongst-strain capsule diversity in three strains of Bacteroides fragilis.
  Microbiology, 156, 3255-3269.  
20150242 V.Malshetty, K.Kurthkoti, A.China, B.Mallick, S.Yamunadevi, P.B.Sang, N.Srinivasan, V.Nagaraja, and U.Varshney (2010).
Novel insertion and deletion mutants of RpoB that render Mycobacterium smegmatis RNA polymerase resistant to rifampicin-mediated inhibition of transcription.
  Microbiology, 156, 1565-1573.  
19182995 A.B.Smith, and S.Dong (2009).
An efficient, second-generation synthesis of the signature dioxabicyclo[3.2.1]octane core of (+)-sorangicin A and elaboration of the (Z,Z,E)-triene acid system.
  Org Lett, 11, 1099-1102.  
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.  
19896365 D.G.Vassylyev (2009).
Elongation by RNA polymerase: a race through roadblocks.
  Curr Opin Struct Biol, 19, 691-700.  
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.  
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.  
19266075 R.C.MacLean, and A.Buckling (2009).
The distribution of fitness effects of beneficial mutations in Pseudomonas aeruginosa.
  PLoS Genet, 5, e1000406.  
18045873 A.Rutkowska, M.P.Mayer, A.Hoffmann, F.Merz, B.Zachmann-Brand, C.Schaffitzel, N.Ban, E.Deuerling, and B.Bukau (2008).
Dynamics of trigger factor interaction with translating ribosomes.
  J Biol Chem, 283, 4124-4132.  
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
18280161 S.Borukhov, and E.Nudler (2008).
RNA polymerase: the vehicle of transcription.
  Trends Microbiol, 16, 126-134.  
18679430 V.Svetlov, and E.Nudler (2008).
Jamming the ratchet of transcription.
  Nat Struct Mol Biol, 15, 777-779.  
17407127 M.Kopp, C.Rupprath, H.Irschik, A.Bechthold, L.Elling, and R.Müller (2007).
SorF: a glycosyltransferase with promiscuous donor substrate specificity in vitro.
  Chembiochem, 8, 813-819.  
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.  
16096056 I.Artsimovitch, M.N.Vassylyeva, D.Svetlov, V.Svetlov, A.Perederina, N.Igarashi, N.Matsugaki, S.Wakatsuki, T.H.Tahirov, and D.G.Vassylyev (2005).
Allosteric modulation of the RNA polymerase catalytic reaction is an essential component of transcription control by rifamycins.
  Cell, 122, 351-363.
PDB codes: 2a68 2a69 2a6e 2a6f 2a6g
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
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.

 

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