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PDBsum entry 2a6f
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Toxin PDB id
2a6f

 

 

 

 

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Contents
Protein chain
335 a.a.
Theoretical model
PDB id:
2a6f
Name: Toxin
Title: Three dimensional structure of leucine rich repeat protein1(lrim1) of anopheles gambiae.
Structure: Leucine rich repeat protein1(lrim1). Chain: a
Source: Anopheles gambiae str. Pest. Strain: pest
Authors: B.Shanmugapriya,K.Thiyagesan,K.Gunasekaran
Key ref:
I.Artsimovitch et al. (2005). Allosteric modulation of the RNA polymerase catalytic reaction is an essential component of transcription control by rifamycins. Cell, 122, 351-363. PubMed id: 16096056 DOI: 10.1016/j.cell.2005.07.014
Date:
02-Jul-05     Release date:   25-Oct-05    
PROCHECK
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 Headers
 References

Protein chain
No UniProt id for this chain
Struc: 335 a.a.
Key:    Secondary structure

 

 
DOI no: 10.1016/j.cell.2005.07.014 Cell 122:351-363 (2005)
PubMed id: 16096056  
 
 
Allosteric modulation of the RNA polymerase catalytic reaction is an essential component of transcription control by rifamycins.
I.Artsimovitch, M.N.Vassylyeva, D.Svetlov, V.Svetlov, A.Perederina, N.Igarashi, N.Matsugaki, S.Wakatsuki, T.H.Tahirov, D.G.Vassylyev.
 
  ABSTRACT  
 
Rifamycins, the clinically important antibiotics, target bacterial RNA polymerase (RNAP). A proposed mechanism in which rifamycins sterically block the extension of nascent RNA beyond three nucleotides does not alone explain why certain RNAP mutations confer resistance to some but not other rifamycins. Here we show that unlike rifampicin and rifapentin, and contradictory to the steric model, rifabutin inhibits formation of the first and second phosphodiester bonds. We report 2.5 A resolution structures of rifabutin and rifapentin complexed with the Thermus thermophilus RNAP holoenzyme. The structures reveal functionally important distinct interactions of antibiotics with the initiation sigma factor. Strikingly, both complexes lack the catalytic Mg2+ ion observed in the apo-holoenzyme, whereas an increase in Mg2+ concentration confers resistance to rifamycins. We propose that a rifamycin-induced signal is transmitted over approximately 19 A to the RNAP active site to slow down catalysis. Based on structural predictions, we designed enzyme substitutions that apparently interrupt this allosteric signal.
 
  Selected figure(s)  
 
Figure 3.
Figure 3. RNAP/Rifs Binding 		Figure 5.
Figure 5. Increased Levels of Mg^2+ Ion Protect RNAP against Inhibition by Rifs
 
  The above figures are reprinted by permission from Cell Press: Cell (2005, 122, 351-363) copyright 2005.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21393153 G.K.Siu, Y.Zhang, T.C.Lau, R.W.Lau, P.L.Ho, W.W.Yew, S.K.Tsui, V.C.Cheng, K.Y.Yuen, and W.C.Yam (2011).
Mutations outside the rifampicin resistance-determining region associated with rifampicin resistance in Mycobacterium tuberculosis.
  J Antimicrob Chemother, 66, 730-733.  
19926651 A.Dey, A.K.Verma, and D.Chatterji (2010).
Role of an RNA polymerase interacting protein, MsRbpA, from Mycobacterium smegmatis in phenotypic tolerance to rifampicin.
  Microbiology, 156, 873-883.  
20562828 A.Tupin, M.Gualtieri, J.P.Leonetti, and K.Brodolin (2010).
The transcription inhibitor lipiarmycin blocks DNA fitting into the RNA polymerase catalytic site.
  EMBO J, 29, 2527-2537.  
20929805 H.J.Yoon, J.Kuwabara, J.H.Kim, and C.A.Mirkin (2010).
Allosteric supramolecular triple-layer catalysts.
  Science, 330, 66-69.  
20586560 J.Cottreau, S.F.Baker, H.L.DuPont, and K.W.Garey (2010).
Rifaximin: a nonsystemic rifamycin antibiotic for gastrointestinal infections.
  Expert Rev Anti Infect Ther, 8, 747-760.  
20606072 M.K.Taha, S.T.Hedberg, M.Szatanik, E.Hong, C.Ruckly, R.Abad, S.Bertrand, F.Carion, H.Claus, A.Corso, R.Enríquez, S.Heuberger, W.Hryniewicz, K.A.Jolley, P.Kriz, M.Mollerach, M.Musilek, A.Neri, P.Olcén, M.Pana, A.Skoczynska, C.Sorhouet Pereira, P.Stefanelli, G.Tzanakaki, M.Unemo, J.A.Vázquez, U.Vogel, and I.Wasko (2010).
Multicenter study for defining the breakpoint for rifampin resistance in Neisseria meningitidis by rpoB sequencing.
  Antimicrob Agents Chemother, 54, 3651-3658.  
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.  
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.  
18946472 G.A.Belogurov, M.N.Vassylyeva, A.Sevostyanova, J.R.Appleman, A.X.Xiang, R.Lira, S.E.Webber, S.Klyuyev, E.Nudler, I.Artsimovitch, and D.G.Vassylyev (2009).
Transcription inactivation through local refolding of the RNA polymerase structure.
  Nature, 457, 332-335.
PDB code: 3eql
19170875 I.Flåtten, Morigen, and K.Skarstad (2009).
DnaA protein interacts with RNA polymerase and partially protects it from the effect of rifampicin.
  Mol Microbiol, 71, 1018-1030.  
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.  
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.  
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
18443108 G.T.Robertson, E.J.Bonventre, T.B.Doyle, Q.Du, L.Duncan, T.W.Morris, E.D.Roche, D.Yan, and A.S.Lynch (2008).
In vitro evaluation of CBR-2092, a novel rifamycin-quinolone hybrid antibiotic: studies of the mode of action in Staphylococcus aureus.
  Antimicrob Agents Chemother, 52, 2313-2323.  
  17666783 A.Szalewska-Palasz, G.Wegrzyn, and A.Wegrzyn (2007).
Mechanisms of physiological regulation of RNA synthesis in bacteria: new discoveries breaking old schemes.
  J Appl Genet, 48, 281-294.  
17711918 V.Svetlov, G.A.Belogurov, E.Shabrova, D.G.Vassylyev, and I.Artsimovitch (2007).
Allosteric control of the RNA polymerase by the elongation factor RfaH.
  Nucleic Acids Res, 35, 5694-5705.  
16690607 A.Kulbachinskiy, and A.Mustaev (2006).
Region 3.2 of the sigma subunit contributes to the binding of the 3'-initiating nucleotide in the RNA polymerase active center and facilitates promoter clearance during initiation.
  J Biol Chem, 281, 18273-18276.  
16942902 J.Davies, G.B.Spiegelman, and G.Yim (2006).
The world of subinhibitory antibiotic concentrations.
  Curr Opin Microbiol, 9, 445-453.  
16629670 K.V.Newell, D.P.Thomas, D.Brekasis, and M.S.Paget (2006).
The RNA polymerase-binding protein RbpA confers basal levels of rifampicin resistance on Streptomyces coelicolor.
  Mol Microbiol, 60, 687-696.  
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.  
16273103 D.G.Vassylyev, V.Svetlov, M.N.Vassylyeva, A.Perederina, N.Igarashi, N.Matsugaki, S.Wakatsuki, and I.Artsimovitch (2005).
Structural basis for transcription inhibition by tagetitoxin.
  Nat Struct Mol Biol, 12, 1086-1093.
PDB code: 2be5
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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