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115 a.a.
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116 a.a.
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130 a.a.
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* Residue conservation analysis
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PDB id:
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Transcription
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Title:
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Apo-nikr
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Structure:
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Nickel responsive regulator. Chain: a, b, c, d. Synonym: nikr. Engineered: yes
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Source:
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Escherichia coli. Organism_taxid: 562. Gene: nikr. Expressed in: escherichia coli. Expression_system_taxid: 562.
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Biol. unit:
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Tetramer (from
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Resolution:
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2.30Å
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R-factor:
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0.248
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R-free:
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0.305
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Authors:
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E.R.Schreiter,M.D.Sintchak,Y.Guo,P.T.Chivers,R.T.Sauer,C.L.Drennan
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Key ref:
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E.R.Schreiter
et al.
(2003).
Crystal structure of the nickel-responsive transcription factor NikR.
Nat Struct Biol,
10,
794-799.
PubMed id:
DOI:
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Date:
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11-Aug-03
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Release date:
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30-Sep-03
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PROCHECK
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Headers
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References
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P0A6Z6
(NIKR_ECOLI) -
Nickel-responsive regulator from Escherichia coli (strain K12)
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Seq:
Struc:
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133 a.a.
115 a.a.
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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 Biol
10:794-799
(2003)
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PubMed id:
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Crystal structure of the nickel-responsive transcription factor NikR.
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E.R.Schreiter,
M.D.Sintchak,
Y.Guo,
P.T.Chivers,
R.T.Sauer,
C.L.Drennan.
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ABSTRACT
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NikR is a metal-responsive transcription factor that controls nickel uptake in
Escherichia coli by regulating expression of a nickel-specific ATP-binding
cassette (ABC) transporter. We have determined the first two structures of NikR:
the full-length apo repressor at a resolution of 2.3 A and the nickel-bound
C-terminal regulatory domain at a resolution of 1.4 A. NikR is the only known
metal-responsive member of the ribbon-helix-helix family of transcription
factors, and its structure has a quaternary arrangement consisting of two
dimeric DNA-binding domains separated by a tetrameric regulatory domain that
binds nickel. The position of the C-terminal regulatory domain enforces a large
spacing between the contacts that each NikR DNA-binding domain can make with the
nik operator. The regulatory domain of NikR contains four nickel-binding sites
at the tetramer interface, each exhibiting a novel square-planar coordination by
three histidines and one cysteine side chain.
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Selected figure(s)
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Figure 1.
Figure 1. NikR structures and structural comparisons. (a)
Ribbon diagram of the apo-NikR tetramer colored by polypeptide
chain. Domains are bracketed and labeled as either
ribbon-helix-helix (DNA-binding domain) or Ni-regulatory domain
(C domain). Secondary structure elements of the blue NikR
monomer are labeled. (b) Superposition of the C  traces
of the regulatory domain of apo NikR (light gray) and
nickel-bound C domain (colored by polypeptide chain) based on
all common C positions.
Nickel atoms from the nickel-bound C-domain structure are cyan
spheres. The most similar regions are the  -strands
of the central -sheets,
whereas the most substantial differences are in the loop
(labeled with an asterisk near the green monomer) and helix 3.
Note the absence of this helix in the three other apo NikR
molecules. (c) Two monomers of the nickel-bound C-domain
tetramer shown as ribbon diagrams and colored by chain. Amino
acid side chains ligating nickel are shown in ball-and-stick and
colored by atom type (carbon atoms from the two monomers are
green and gray, respectively) and nickel is a cyan sphere. (d)
Regulatory domain of PGDH (from 1PSD) shown as in c. Bound
serine is in cyan ball-and-stick. Note the similarity in
location of bound allosteric ligand and the contribution to
binding of each ligand from different monomers across their
interface. All figures were prepared using Ribbons30.
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Figure 3.
Figure 3. Side chain movements and interactions at the
high-affinity nickel site. (a) Comparison of the nickel
ligands between apo NikR and nickel-bound C domain after
superposition of all common C atoms
of each tetramer. Amino acid side chains of the nickel ligands
are in ball-and-stick, with carbon atoms green for the
nickel-bound C-domain structure and white for the apo NikR
structure. Nickel ions, cyan spheres; nickel-ligand bonds, gray
lines. (b) Hydrogen bond network between two nickel-binding
sites in the nickel-bound C-domain structure. Amino acid side
chains of two molecules of the NikR regulatory domain are in
ball-and-stick with gray or green carbon atoms, respectively.
Dashed lines indicate hydrogen bonds.
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The above figures are
reprinted
by permission from Macmillan Publishers Ltd:
Nat Struct Biol
(2003,
10,
794-799)
copyright 2003.
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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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N.Chopra,
S.Agarwal,
S.Verma,
S.Bhatnagar,
and
R.Bhatnagar
(2011).
Modeling of the structure and interactions of the B. anthracis antitoxin, MoxX: deletion mutant studies highlight its modular structure and repressor function.
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J Comput Aided Mol Des,
25,
275-291.
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Y.B.Zeng,
N.Yang,
and
H.Sun
(2011).
Metal-binding properties of an hpn-like histidine-rich protein.
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Chemistry,
17,
5852-5860.
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C.Bahlawane,
C.Dian,
C.Muller,
A.Round,
C.Fauquant,
K.Schauer,
H.de Reuse,
L.Terradot,
and
I.Michaud-Soret
(2010).
Structural and mechanistic insights into Helicobacter pylori NikR activation.
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Nucleic Acids Res,
38,
3106-3118.
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PDB codes:
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C.M.Phillips,
C.M.Stultz,
and
C.L.Drennan
(2010).
Searching for the Nik operon: how a ligand-responsive transcription factor hunts for its DNA binding site.
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Biochemistry,
49,
7757-7763.
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C.M.Phillips,
E.R.Schreiter,
C.M.Stultz,
and
C.L.Drennan
(2010).
Structural basis of low-affinity nickel binding to the nickel-responsive transcription factor NikR from Escherichia coli.
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Biochemistry,
49,
7830-7838.
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PDB code:
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E.L.Benanti,
and
P.T.Chivers
(2010).
Geobacter uraniireducens NikR displays a DNA binding mode distinct from other members of the NikR family.
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J Bacteriol,
192,
4327-4336.
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J.S.Iwig,
and
P.T.Chivers
(2010).
Coordinating intracellular nickel-metal-site structure-function relationships and the NikR and RcnR repressors.
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Nat Prod Rep,
27,
658-667.
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D.J.Sindhikara,
A.E.Roitberg,
and
K.M.Merz
(2009).
Apo and nickel-bound forms of the Pyrococcus horikoshii species of the metalloregulatory protein: NikR characterized by molecular dynamics simulations.
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Biochemistry,
48,
12024-12033.
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F.Guillière,
N.Peixeiro,
A.Kessler,
B.Raynal,
N.Desnoues,
J.Keller,
M.Delepierre,
D.Prangishvili,
G.Sezonov,
and
J.I.Guijarro
(2009).
Structure, function, and targets of the transcriptional regulator SvtR from the hyperthermophilic archaeal virus SIRV1.
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J Biol Chem,
284,
22222-22237.
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PDB code:
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J.Siltberg-Liberles,
and
A.Martinez
(2009).
Searching distant homologs of the regulatory ACT domain in phenylalanine hydroxylase.
|
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Amino Acids,
36,
235-249.
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J.W.Taraska,
M.C.Puljung,
N.B.Olivier,
G.E.Flynn,
and
W.N.Zagotta
(2009).
Mapping the structure and conformational movements of proteins with transition metal ion FRET.
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Nat Methods,
6,
532-537.
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PDB codes:
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L.Ni,
S.O.Jensen,
N.Ky Tonthat,
T.Berg,
S.M.Kwong,
F.H.Guan,
M.H.Brown,
R.A.Skurray,
N.Firth,
and
M.A.Schumacher
(2009).
The Staphylococcus aureus pSK41 plasmid-encoded ArtA protein is a master regulator of plasmid transmission genes and contains a RHH motif used in alternate DNA-binding modes.
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Nucleic Acids Res,
37,
6970-6983.
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PDB code:
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R.M.Jenkins,
M.L.Singleton,
E.Almaraz,
J.H.Reibenspies,
and
M.Y.Darensbourg
(2009).
Imidazole-containing (N3S)-Ni(II) complexes relating to nickel containing biomolecules.
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Inorg Chem,
48,
7280-7293.
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S.C.Dodani,
Q.He,
and
C.J.Chang
(2009).
A turn-on fluorescent sensor for detecting nickel in living cells.
|
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J Am Chem Soc,
131,
18020-18021.
|
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S.C.Wang,
A.V.Dias,
and
D.B.Zamble
(2009).
The "metallo-specific" response of proteins: a perspective based on the Escherichia coli transcriptional regulator NikR.
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Dalton Trans,
(),
2459-2466.
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Z.Ma,
F.E.Jacobsen,
and
D.P.Giedroc
(2009).
Coordination chemistry of bacterial metal transport and sensing.
|
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Chem Rev,
109,
4644-4681.
|
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G.Cui,
and
K.M.Merz
(2008).
The intrinsic dynamics and function of nickel-binding regulatory protein: insights from elastic network analysis.
|
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Biophys J,
94,
3769-3778.
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J.S.Iwig,
S.Leitch,
R.W.Herbst,
M.J.Maroney,
and
P.T.Chivers
(2008).
Ni(II) and Co(II) sensing by Escherichia coli RcnR.
|
| |
J Am Chem Soc,
130,
7592-7606.
|
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|
|
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|
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P.R.Chen,
and
C.He
(2008).
Selective recognition of metal ions by metalloregulatory proteins.
|
| |
Curr Opin Chem Biol,
12,
214-221.
|
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|
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R.E.Diederix,
C.Fauquant,
A.Rodrigue,
M.A.Mandrand-Berthelot,
and
I.Michaud-Soret
(2008).
Sub-micromolar affinity of Escherichia coli NikR for Ni(II).
|
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Chem Commun (Camb),
(),
1813-1815.
|
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S.Cun,
H.Li,
R.Ge,
M.C.Lin,
and
H.Sun
(2008).
A histidine-rich and cysteine-rich metal-binding domain at the C terminus of heat shock protein A from Helicobacter pylori: implication for nickel homeostasis and bismuth susceptibility.
|
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J Biol Chem,
283,
15142-15151.
|
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Y.B.Zeng,
D.M.Zhang,
H.Li,
and
H.Sun
(2008).
Binding of Ni2+ to a histidine- and glutamine-rich protein, Hpn-like.
|
| |
J Biol Inorg Chem,
13,
1121-1131.
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B.Zambelli,
M.Bellucci,
A.Danielli,
V.Scarlato,
and
S.Ciurli
(2007).
The Ni2+ binding properties of Helicobacter pylori NikR.
|
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Chem Commun (Camb),
(),
3649-3651.
|
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|
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|
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D.P.Giedroc,
and
A.I.Arunkumar
(2007).
Metal sensor proteins: nature's metalloregulated allosteric switches.
|
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Dalton Trans,
(),
3107-3120.
|
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|
|
|
|
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E.L.Benanti,
and
P.T.Chivers
(2007).
The N-terminal arm of the Helicobacter pylori Ni2+-dependent transcription factor NikR is required for specific DNA binding.
|
| |
J Biol Chem,
282,
20365-20375.
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G.Shen,
R.Balasubramanian,
T.Wang,
Y.Wu,
L.M.Hoffart,
C.Krebs,
D.A.Bryant,
and
J.H.Golbeck
(2007).
SufR coordinates two [4Fe-4S]2+, 1+ clusters and functions as a transcriptional repressor of the sufBCDS operon and an autoregulator of sufR in cyanobacteria.
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J Biol Chem,
282,
31909-31919.
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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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D.A.Rodionov,
P.Hebbeln,
M.S.Gelfand,
and
T.Eitinger
(2006).
Comparative and functional genomic analysis of prokaryotic nickel and cobalt uptake transporters: evidence for a novel group of ATP-binding cassette transporters.
|
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J Bacteriol,
188,
317-327.
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E.R.Schreiter,
S.C.Wang,
D.B.Zamble,
and
C.L.Drennan
(2006).
NikR-operator complex structure and the mechanism of repressor activation by metal ions.
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Proc Natl Acad Sci U S A,
103,
13676-13681.
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PDB codes:
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G.A.Grant
(2006).
The ACT domain: a small molecule binding domain and its role as a common regulatory element.
|
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J Biol Chem,
281,
33825-33829.
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J.D.Larson,
J.L.Jenkins,
J.P.Schuermann,
Y.Zhou,
D.F.Becker,
and
J.J.Tanner
(2006).
Crystal structures of the DNA-binding domain of Escherichia coli proline utilization A flavoprotein and analysis of the role of Lys9 in DNA recognition.
|
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Protein Sci,
15,
2630-2641.
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PDB codes:
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J.I.Kliegman,
S.L.Griner,
J.D.Helmann,
R.G.Brennan,
and
A.Glasfeld
(2006).
Structural basis for the metal-selective activation of the manganese transport regulator of Bacillus subtilis.
|
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Biochemistry,
45,
3493-3505.
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PDB codes:
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L.Wolfram,
E.Haas,
and
P.Bauerfeind
(2006).
Nickel represses the synthesis of the nickel permease NixA of Helicobacter pylori.
|
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J Bacteriol,
188,
1245-1250.
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N.S.Dosanjh,
and
S.L.Michel
(2006).
Microbial nickel metalloregulation: NikRs for nickel ions.
|
| |
Curr Opin Chem Biol,
10,
123-130.
|
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|
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A.V.Dias,
and
D.B.Zamble
(2005).
Protease digestion analysis of Escherichia coli NikR: evidence for conformational stabilization with Ni(II).
|
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J Biol Inorg Chem,
10,
605-612.
|
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|
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C.Rensing
(2005).
Form and function in metal-dependent transcriptional regulation: dawn of the enlightenment.
|
| |
J Bacteriol,
187,
3909-3912.
|
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|
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|
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E.Carmelo,
D.Barillà,
A.P.Golovanov,
L.Y.Lian,
A.Derome,
and
F.Hayes
(2005).
The unstructured N-terminal tail of ParG modulates assembly of a quaternary nucleoprotein complex in transcription repression.
|
| |
J Biol Chem,
280,
28683-28691.
|
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|
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E.Soler,
A.Le Saux,
F.Guinut,
B.Passet,
R.Cohen,
C.Merle,
A.Charpilienne,
C.Fourgeux,
V.Sorel,
A.Piriou,
I.Schwartz-Cornil,
J.Cohen,
and
L.M.Houdebine
(2005).
Production of two vaccinating recombinant rotavirus proteins in the milk of transgenic rabbits.
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Transgenic Res,
14,
833-844.
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F.D.Ernst,
E.J.Kuipers,
A.Heijens,
R.Sarwari,
J.Stoof,
C.W.Penn,
J.G.Kusters,
and
A.H.van Vliet
(2005).
The nickel-responsive regulator NikR controls activation and repression of gene transcription in Helicobacter pylori.
|
| |
Infect Immun,
73,
7252-7258.
|
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|
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I.Delany,
R.Ieva,
A.Soragni,
M.Hilleringmann,
R.Rappuoli,
and
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(2005).
In vitro analysis of protein-operator interactions of the NikR and fur metal-responsive regulators of coregulated genes in Helicobacter pylori.
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J Bacteriol,
187,
7703-7715.
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K.Welfle,
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R.Misselwitz,
J.Behlke,
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and
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(2005).
Role of the N-terminal region and of beta-sheet residue Thr29 on the activity of the omega2 global regulator from the broad-host range Streptococcus pyogenes plasmid pSM19035.
|
| |
Biol Chem,
386,
881-894.
|
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L.Malphettes,
C.C.Weber,
M.D.El-Baba,
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W.Weber,
and
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(2005).
A novel mammalian expression system derived from components coordinating nicotine degradation in arthrobacter nicotinovorans pAO1.
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Nucleic Acids Res,
33,
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M.A.Pennella,
and
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(2005).
Structural determinants of metal selectivity in prokaryotic metal-responsive transcriptional regulators.
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Biometals,
18,
413-428.
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S.Dey,
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and
J.C.Sacchettini
(2005).
Crystal structure of Mycobacterium tuberculosis D-3-phosphoglycerate dehydrogenase: extreme asymmetry in a tetramer of identical subunits.
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| |
J Biol Chem,
280,
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|
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PDB code:
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T.Kitao,
C.Kuroishi,
and
T.H.Tahirov
(2005).
Crystallization and preliminary crystallographic analysis of the nickel-responsive regulator NikR from Pyrococcus horikoshii.
|
| |
Acta Crystallogr Sect F Struct Biol Cryst Commun,
61,
43-45.
|
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A.B.de la Hoz,
F.Pratto,
R.Misselwitz,
C.Speck,
W.Weihofen,
K.Welfle,
W.Saenger,
H.Welfle,
and
J.C.Alonso
(2004).
Recognition of DNA by omega protein from the broad-host range Streptococcus pyogenes plasmid pSM19035: analysis of binding to operator DNA with one to four heptad repeats.
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| |
Nucleic Acids Res,
32,
3136-3147.
|
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D.Gu,
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V.Kallhoff,
B.Baban,
J.J.Tanner,
and
D.F.Becker
(2004).
Identification and characterization of the DNA-binding domain of the multifunctional PutA flavoenzyme.
|
| |
J Biol Chem,
279,
31171-31176.
|
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|
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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
codes are
shown on the right.
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Links
