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* Residue conservation analysis
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Enzyme class:
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Chains A, B, C, D:
E.C.?
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DOI no:
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Nat Struct Mol Biol
12:327-331
(2005)
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PubMed id:
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Crystal structure of archaeal toxin-antitoxin RelE-RelB complex with implications for toxin activity and antitoxin effects.
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H.Takagi,
Y.Kakuta,
T.Okada,
M.Yao,
I.Tanaka,
M.Kimura.
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ABSTRACT
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The Escherichia coli chromosome encodes toxin-antitoxin pairs. The toxin RelE
cleaves mRNA positioned at the A-site in ribosomes, whereas the antitoxin RelB
relieves the effect of RelE. The hyperthermophilic archaeon Pyrococcus
horikoshii OT3 has the archaeal homologs aRelE and aRelB. Here we report the
crystal structure of aRelE in complex with aRelB determined at a resolution of
2.3 A. aRelE folds into an alpha/beta structure, whereas aRelB lacks a distinct
hydrophobic core and extensively wraps around the molecular surface of aRelE.
Neither component shows structural homology to known ribonucleases or their
inhibitors. Site-directed mutagenesis suggests that Arg85, in the C-terminal
region, is strongly involved in the functional activity of aRelE, whereas Arg40,
Leu48, Arg58 and Arg65 play a modest role in the toxin's activity.
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Selected figure(s)
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Figure 1.
Figure 1. Structures of aRelB and aRelE. (a) Ribbon
representation of the aRelB -aRelE complex from P. horikoshii.
aRelB (red) is present as a polypeptide chain lacking any
distinct hydrophobic core, and aRelE (green) folds into an  /
 structure.
N and C termini of both molecules are indicated. (b) Stereo view
of the heterotetrameric structure of aRelB and aRelE from P.
horikoshii. Two molecules (A and B) of the aRelB -aRelE complex
observed in the asymmetric unit are indicated. Side chains of
hydrophobic residues at 1
in aRelB are indicated.
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Figure 3.
Figure 3. View of the heterodimer interface between aRelB and
aRelE. Residues involved in the interaction between the
central loop in aRelB and the -sheet
in aRelE are indicated. Selected residues of aRelB (red) and
aRelE (green) are labeled. The hydrogen bonds formed from side
chains are indicated by dashed lines.
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The above figures are
reprinted
by permission from Macmillan Publishers Ltd:
Nat Struct Mol Biol
(2005,
12,
327-331)
copyright 2005.
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Figures were
selected
by an automated process.
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Literature references that cite this PDB file's key reference
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PubMed id
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Reference
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T.R.Blower,
G.P.Salmond,
and
B.F.Luisi
(2011).
Balancing at survival's edge: the structure and adaptive benefits of prokaryotic toxin-antitoxin partners.
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Curr Opin Struct Biol,
21,
109-118.
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Y.Zhang,
and
M.Inouye
(2011).
RatA (YfjG), an Escherichia coli toxin, inhibits 70S ribosome association to block translation initiation.
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Mol Microbiol,
79,
1418-1429.
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C.Göbl,
S.Kosol,
T.Stockner,
H.M.Rückert,
and
K.Zangger
(2010).
Solution structure and membrane binding of the toxin fst of the par addiction module.
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Biochemistry,
49,
6567-6575.
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PDB code:
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C.Nieto,
E.Sadowy,
A.G.de la Campa,
W.Hryniewicz,
and
M.Espinosa
(2010).
The relBE2Spn toxin-antitoxin system of Streptococcus pneumoniae: role in antibiotic tolerance and functional conservation in clinical isolates.
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PLoS One,
5,
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L.C.Barbosa,
S.S.Garrido,
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D.B.Delfino,
and
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(2010).
Function inferences from a molecular structural model of bacterial ParE toxin.
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Bioinformation,
4,
438-440.
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M.A.Arbing,
S.K.Handelman,
A.P.Kuzin,
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F.P.Rothenbacher,
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J.M.Hurley,
R.Xiao,
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M.Inouye,
G.T.Montelione,
N.A.Woychik,
and
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(2010).
Crystal structures of Phd-Doc, HigA, and YeeU establish multiple evolutionary links between microbial growth-regulating toxin-antitoxin systems.
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Structure,
18,
996.
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PDB codes:
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M.Christensen-Dalsgaard,
M.G.Jørgensen,
and
K.Gerdes
(2010).
Three new RelE-homologous mRNA interferases of Escherichia coli differentially induced by environmental stresses.
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Mol Microbiol,
75,
333-348.
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M.Uzan,
and
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(2010).
Post-transcriptional control by bacteriophage T4: mRNA decay and inhibition of translation initiation.
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Virol J,
7,
360.
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B.L.Brown,
S.Grigoriu,
Y.Kim,
J.M.Arruda,
A.Davenport,
T.K.Wood,
W.Peti,
and
R.Page
(2009).
Three dimensional structure of the MqsR:MqsA complex: a novel TA pair comprised of a toxin homologous to RelE and an antitoxin with unique properties.
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PLoS Pathog,
5,
e1000706.
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PDB codes:
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C.Kikutake,
M.Shinohara,
H.Takagi,
T.Nakashima,
and
M.Kimura
(2009).
The C-terminal portion of an archaeal toxin, aRelE, plays a crucial role in protein synthesis inhibition.
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Biosci Biotechnol Biochem,
73,
2766-2768.
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C.Neubauer,
Y.G.Gao,
K.R.Andersen,
C.M.Dunham,
A.C.Kelley,
J.Hentschel,
K.Gerdes,
V.Ramakrishnan,
and
D.E.Brodersen
(2009).
The structural basis for mRNA recognition and cleavage by the ribosome-dependent endonuclease RelE.
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Cell,
139,
1084-1095.
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PDB codes:
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E.Diago-Navarro,
L.Mora,
R.H.Buckingham,
R.Díaz-Orejas,
and
M.Lemonnier
(2009).
Novel Escherichia coli RF1 mutants with decreased translation termination activity and increased sensitivity to the cytotoxic effect of the bacterial toxins Kid and RelE.
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Mol Microbiol,
71,
66-78.
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G.Y.Li,
Y.Zhang,
M.Inouye,
and
M.Ikura
(2009).
Inhibitory Mechanism of Escherichia coli RelE-RelB Toxin-Antitoxin Module Involves a Helix Displacement Near an mRNA Interferase Active Site.
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J Biol Chem,
284,
14628-14636.
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PDB codes:
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J.M.Hurley,
and
N.A.Woychik
(2009).
Bacterial Toxin HigB Associates with Ribosomes and Mediates Translation-dependent mRNA Cleavage at A-rich Sites.
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J Biol Chem,
284,
18605-18613.
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L.Miallau,
M.Faller,
J.Chiang,
M.Arbing,
F.Guo,
D.Cascio,
and
D.Eisenberg
(2009).
Structure and Proposed Activity of a Member of the VapBC Family of Toxin-Antitoxin Systems: VapBC-5 FROM MYCOBACTERIUM TUBERCULOSIS.
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J Biol Chem,
284,
276-283.
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PDB code:
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L.Zhu,
K.Inoue,
S.Yoshizumi,
H.Kobayashi,
Y.Zhang,
M.Ouyang,
F.Kato,
M.Sugai,
and
M.Inouye
(2009).
Staphylococcus aureus MazF specifically cleaves a pentad sequence, UACAU, which is unusually abundant in the mRNA for pathogenic adhesive factor SraP.
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J Bacteriol,
191,
3248-3255.
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M.G.Jørgensen,
D.P.Pandey,
M.Jaskolska,
and
K.Gerdes
(2009).
HicA of Escherichia coli defines a novel family of translation-independent mRNA interferases in bacteria and archaea.
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J Bacteriol,
191,
1191-1199.
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M.Overgaard,
J.Borch,
and
K.Gerdes
(2009).
RelB and RelE of Escherichia coli form a tight complex that represses transcription via the ribbon-helix-helix motif in RelB.
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J Mol Biol,
394,
183-196.
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S.B.Korch,
H.Contreras,
and
J.E.Clark-Curtiss
(2009).
Three Mycobacterium tuberculosis Rel toxin-antitoxin modules inhibit mycobacterial growth and are expressed in infected human macrophages.
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J Bacteriol,
191,
1618-1630.
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S.E.Bailey,
and
F.Hayes
(2009).
Influence of operator site geometry on transcriptional control by the YefM-YoeB toxin-antitoxin complex.
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J Bacteriol,
191,
762-772.
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Y.Yamaguchi,
J.H.Park,
and
M.Inouye
(2009).
MqsR, a crucial regulator for quorum sensing and biofilm formation, is a GCU-specific mRNA interferase in Escherichia coli.
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J Biol Chem,
284,
28746-28753.
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Y.Zhang,
and
M.Inouye
(2009).
The Inhibitory Mechanism of Protein Synthesis by YoeB, an Escherichia coli Toxin.
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J Biol Chem,
284,
6627-6638.
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A.Garcia-Pino,
M.Christensen-Dalsgaard,
L.Wyns,
M.Yarmolinsky,
R.D.Magnuson,
K.Gerdes,
and
R.Loris
(2008).
Doc of Prophage P1 Is Inhibited by Its Antitoxin Partner Phd through Fold Complementation.
|
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J Biol Chem,
283,
30821-30827.
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PDB code:
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A.Garcia-Pino,
M.H.Dao-Thi,
E.Gazit,
R.D.Magnuson,
L.Wyns,
and
R.Loris
(2008).
Crystallization of Doc and the Phd-Doc toxin-antitoxin complex.
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Acta Crystallogr Sect F Struct Biol Cryst Commun,
64,
1034-1038.
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D.Andreev,
V.Hauryliuk,
I.Terenin,
S.Dmitriev,
M.Ehrenberg,
and
I.Shatsky
(2008).
The bacterial toxin RelE induces specific mRNA cleavage in the A site of the eukaryote ribosome.
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RNA,
14,
233-239.
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J.Lu,
A.Esberg,
B.Huang,
and
A.S.Byström
(2008).
Kluyveromyces lactis gamma-toxin, a ribonuclease that recognizes the anticodon stem loop of tRNA.
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Nucleic Acids Res,
36,
1072-1080.
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K.D.Han,
S.J.Park,
S.B.Jang,
and
B.J.Lee
(2008).
Solution structure of conserved hypothetical protein HP0892 from Helicobacter pylori.
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Proteins,
70,
599-602.
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PDB code:
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M.Overgaard,
J.Borch,
M.G.Jørgensen,
and
K.Gerdes
(2008).
Messenger RNA interferase RelE controls relBE transcription by conditional cooperativity.
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Mol Microbiol,
69,
841-857.
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A.Pal,
P.Chakrabarti,
R.Bahadur,
F.Rodier,
and
J.Janin
(2007).
Peptide segments in protein-protein interfaces.
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J Biosci,
32,
101-111.
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B.Odaert,
F.Saïda,
P.Aliprandi,
S.Durand,
J.B.Créchet,
R.Guerois,
S.Laalami,
M.Uzan,
and
F.Bontems
(2007).
Structural and functional studies of RegB, a new member of a family of sequence-specific ribonucleases involved in mRNA inactivation on the ribosome.
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J Biol Chem,
282,
2019-2028.
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PDB code:
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E.M.Moritz,
and
P.J.Hergenrother
(2007).
Toxin-antitoxin systems are ubiquitous and plasmid-encoded in vancomycin-resistant enterococci.
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Proc Natl Acad Sci U S A,
104,
311-316.
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M.Kawano,
L.Aravind,
and
G.Storz
(2007).
An antisense RNA controls synthesis of an SOS-induced toxin evolved from an antitoxin.
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Mol Microbiol,
64,
738-754.
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M.Oberer,
K.Zangger,
K.Gruber,
and
W.Keller
(2007).
The solution structure of ParD, the antidote of the ParDE toxin antitoxin module, provides the structural basis for DNA and toxin binding.
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Protein Sci,
16,
1676-1688.
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PDB code:
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O.Schmidt,
V.J.Schuenemann,
N.J.Hand,
T.J.Silhavy,
J.Martin,
A.N.Lupas,
and
S.Djuranovic
(2007).
prlF and yhaV encode a new toxin-antitoxin system in Escherichia coli.
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J Mol Biol,
372,
894-905.
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R.Motiejūnaite,
J.Armalyte,
A.Markuckas,
and
E.Suziedeliene
(2007).
Escherichia coli dinJ-yafQ genes act as a toxin-antitoxin module.
|
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FEMS Microbiol Lett,
268,
112-119.
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Z.Fu,
N.P.Donegan,
G.Memmi,
and
A.L.Cheung
(2007).
Characterization of MazFSa, an endoribonuclease from Staphylococcus aureus.
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J Bacteriol,
189,
8871-8879.
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C.Condon
(2006).
Shutdown decay of mRNA.
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Mol Microbiol,
61,
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C.Nieto,
T.Pellicer,
D.Balsa,
S.K.Christensen,
K.Gerdes,
and
M.Espinosa
(2006).
The chromosomal relBE2 toxin-antitoxin locus of Streptococcus pneumoniae: characterization and use of a bioluminescence resonance energy transfer assay to detect toxin-antitoxin interaction.
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Mol Microbiol,
59,
1280-1296.
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H.Engelberg-Kulka,
S.Amitai,
I.Kolodkin-Gal,
and
R.Hazan
(2006).
Bacterial programmed cell death and multicellular behavior in bacteria.
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PLoS Genet,
2,
e135.
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K.Mattison,
J.S.Wilbur,
M.So,
and
R.G.Brennan
(2006).
Structure of FitAB from Neisseria gonorrhoeae bound to DNA reveals a tetramer of toxin-antitoxin heterodimers containing pin domains and ribbon-helix-helix motifs.
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J Biol Chem,
281,
37942-37951.
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PDB codes:
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M.Inouye
(2006).
The discovery of mRNA interferases: implication in bacterial physiology and application to biotechnology.
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J Cell Physiol,
209,
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D.N.Wilson,
and
K.H.Nierhaus
(2005).
RelBE or not to be.
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Nat Struct Mol Biol,
12,
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I.Cherny,
L.Rockah,
and
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(2005).
The YoeB toxin is a folded protein that forms a physical complex with the unfolded YefM antitoxin. Implications for a structural-based differential stability of toxin-antitoxin systems.
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J Biol Chem,
280,
30063-30072.
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K.D.Han,
S.J.Park,
S.B.Jang,
W.S.Son,
and
B.J.Lee
(2005).
Solution structure of conserved hypothetical protein HP0894 from Helicobacter pylori.
|
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Proteins,
61,
1114-1116.
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PDB code:
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K.Kamada,
and
F.Hanaoka
(2005).
Conformational change in the catalytic site of the ribonuclease YoeB toxin by YefM antitoxin.
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Mol Cell,
19,
497-509.
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PDB codes:
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Y.Zhang,
L.Zhu,
J.Zhang,
and
M.Inouye
(2005).
Characterization of ChpBK, an mRNA interferase from Escherichia coli.
|
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J Biol Chem,
280,
26080-26088.
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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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Links
