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DNA binding protein
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PDB id
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1cg7
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Contents |
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* Residue conservation analysis
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Gene Ontology (GO) functional annotation
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Cellular component
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nucleus
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2 terms
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Biological process
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response to DNA damage stimulus
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9 terms
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Biochemical function
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protein binding
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5 terms
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DOI no:
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EMBO J
18:2563-2579
(1999)
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PubMed id:
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Solution structure of the HMG protein NHP6A and its interaction with DNA reveals the structural determinants for non-sequence-specific binding.
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F.H.Allain,
Y.M.Yen,
J.E.Masse,
P.Schultze,
T.Dieckmann,
R.C.Johnson,
J.Feigon.
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ABSTRACT
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NHP6A is a chromatin-associated protein from Saccharomyces cerevisiae belonging
to the HMG1/2 family of non-specific DNA binding proteins. NHP6A has only one
HMG DNA binding domain and forms relatively stable complexes with DNA. We have
determined the solution structure of NHP6A and constructed an NMR-based model
structure of the DNA complex. The free NHP6A folds into an L-shaped three
alpha-helix structure, and contains an unstructured 17 amino acid basic tail
N-terminal to the HMG box. Intermolecular NOEs assigned between NHP6A and a 15
bp 13C,15N-labeled DNA duplex containing the SRY recognition sequence have
positioned the NHP6A HMG domain onto the minor groove of the DNA at a site that
is shifted by 1 bp and in reverse orientation from that found in the SRY-DNA
complex. In the model structure of the NHP6A-DNA complex, the N-terminal basic
tail is wrapped around the major groove in a manner mimicking the C-terminal
tail of LEF1. The DNA in the complex is severely distorted and contains two
adjacent kinks where side chains of methionine and phenylalanine that are
important for bending are inserted. The NHP6A-DNA model structure provides
insight into how this class of architectural DNA binding proteins may select
preferential binding sites.
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Selected figure(s)
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The above figure is
reprinted
from an Open Access publication published by Macmillan Publishers Ltd:
EMBO J
(1999,
18,
2563-2579)
copyright 1999.
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Figure was
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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D.Musumeci,
E.M.Bucci,
G.N.Roviello,
R.Sapio,
M.Valente,
M.Moccia,
M.E.Bianchi,
and
C.Pedone
(2011).
DNA-based strategies for blocking HMGB1 cytokine activity: design, synthesis and preliminary in vitro/in vivo assays of DNA and DNA-like duplexes.
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Mol Biosyst, 7,
1742-1752.
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Q.W.Yang,
F.L.Lu,
Y.Zhou,
L.Wang,
Q.Zhong,
S.Lin,
J.Xiang,
J.C.Li,
C.Q.Fang,
and
J.Z.Wang
(2011).
HMBG1 mediates ischemia-reperfusion injury by TRIF-adaptor independent Toll-like receptor 4 signaling.
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J Cereb Blood Flow Metab, 31,
593-605.
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D.J.Stillman
(2010).
Nhp6: a small but powerful effector of chromatin structure in Saccharomyces cerevisiae.
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Biochim Biophys Acta, 1799,
175-180.
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N.L.Dowell,
A.S.Sperling,
M.J.Mason,
and
R.C.Johnson
(2010).
Chromatin-dependent binding of the S. cerevisiae HMGB protein Nhp6A affects nucleosome dynamics and transcription.
|
| |
Genes Dev, 24,
2031-2042.
|
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H.Xin,
S.Takahata,
M.Blanksma,
L.McCullough,
D.J.Stillman,
and
T.Formosa
(2009).
yFACT induces global accessibility of nucleosomal DNA without H2A-H2B displacement.
|
| |
Mol Cell, 35,
365-376.
|
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|
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J.A.Hanover,
D.C.Love,
and
W.A.Prinz
(2009).
Calmodulin-driven Nuclear Entry: Trigger for Sex Determination and Terminal Differentiation.
|
| |
J Biol Chem, 284,
12593-12597.
|
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|
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N.T.Sebastian,
E.M.Bystry,
N.A.Becker,
and
L.J.Maher
(2009).
Enhancement of DNA flexibility in vitro and in vivo by HMGB box A proteins carrying box B residues.
|
| |
Biochemistry, 48,
2125-2134.
|
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S.Ray,
and
A.Grove
(2009).
The yeast high mobility group protein HMO2, a subunit of the chromatin-remodeling complex INO80, binds DNA ends.
|
| |
Nucleic Acids Res, 37,
6389-6399.
|
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I.Tessmer,
Y.Yang,
J.Zhai,
C.Du,
P.Hsieh,
M.M.Hingorani,
and
D.A.Erie
(2008).
Mechanism of MutS Searching for DNA Mismatches and Signaling Repair.
|
| |
J Biol Chem, 283,
36646-36654.
|
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|
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J.Zimmerman,
and
L.J.Maher
(2008).
Transient HMGB protein interactions with B-DNA duplexes and complexes.
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Biochem Biophys Res Commun, 371,
79-84.
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N.A.Becker,
J.D.Kahn,
and
L.J.Maher
(2008).
Eukaryotic HMGB proteins as replacements for HU in E. coli repression loop formation.
|
| |
Nucleic Acids Res, 36,
4009-4021.
|
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|
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T.Stuwe,
M.Hothorn,
E.Lejeune,
V.Rybin,
M.Bortfeld,
K.Scheffzek,
and
A.G.Ladurner
(2008).
The FACT Spt16 "peptidase" domain is a histone H3-H4 binding module.
|
| |
Proc Natl Acad Sci U S A, 105,
8884-8889.
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PDB codes:
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G.Faraco,
S.Fossati,
M.E.Bianchi,
M.Patrone,
M.Pedrazzi,
B.Sparatore,
F.Moroni,
and
A.Chiarugi
(2007).
High mobility group box 1 protein is released by neural cells upon different stresses and worsens ischemic neurodegeneration in vitro and in vivo.
|
| |
J Neurochem, 103,
590-603.
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G.A.Kassavetis,
and
D.F.Steiner
(2006).
Nhp6 is a transcriptional initiation fidelity factor for RNA polymerase III transcription in vitro and in vivo.
|
| |
J Biol Chem, 281,
7445-7451.
|
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P.Aliahmad,
and
J.Kaye
(2006).
Commitment issues: linking positive selection signals and lineage diversification in the thymus.
|
| |
Immunol Rev, 209,
253-273.
|
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S.Briquet,
C.Boschet,
M.Gissot,
E.Tissandié,
E.Sevilla,
J.F.Franetich,
I.Thiery,
Z.Hamid,
C.Bourgouin,
and
C.Vaquero
(2006).
High-mobility-group box nuclear factors of Plasmodium falciparum.
|
| |
Eukaryot Cell, 5,
672-682.
|
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|
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S.McGowan,
A.M.Buckle,
J.A.Irving,
P.C.Ong,
T.A.Bashtannyk-Puhalovich,
W.T.Kan,
K.N.Henderson,
Y.A.Bulynko,
E.Y.Popova,
A.I.Smith,
S.P.Bottomley,
J.Rossjohn,
S.A.Grigoryev,
R.N.Pike,
and
J.C.Whisstock
(2006).
X-ray crystal structure of MENT: evidence for functional loop-sheet polymers in chromatin condensation.
|
| |
EMBO J, 25,
3144-3155.
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PDB codes:
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C.Y.Chen,
T.P.Ko,
T.W.Lin,
C.C.Chou,
C.J.Chen,
and
A.H.Wang
(2005).
Probing the DNA kink structure induced by the hyperthermophilic chromosomal protein Sac7d.
|
| |
Nucleic Acids Res, 33,
430-438.
|
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PDB codes:
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G.A.Kassavetis,
E.Soragni,
R.Driscoll,
and
E.P.Geiduschek
(2005).
Reconfiguring the connectivity of a multiprotein complex: fusions of yeast TATA-binding protein with Brf1, and the function of transcription factor IIIB.
|
| |
Proc Natl Acad Sci U S A, 102,
15406-15411.
|
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|
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M.McCauley,
P.R.Hardwidge,
L.J.Maher,
and
M.C.Williams
(2005).
Dual binding modes for an HMG domain from human HMGB2 on DNA.
|
| |
Biophys J, 89,
353-364.
|
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|
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N.Kasai,
Y.Tsunaka,
I.Ohki,
S.Hirose,
K.Morikawa,
and
S.Tate
(2005).
Solution structure of the HMG-box domain in the SSRP1 subunit of FACT.
|
| |
J Biomol NMR, 32,
83-88.
|
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PDB code:
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S.Giavara,
E.Kosmidou,
M.P.Hande,
M.E.Bianchi,
A.Morgan,
F.d'Adda di Fagagna,
and
S.P.Jackson
(2005).
Yeast Nhp6A/B and mammalian Hmgb1 facilitate the maintenance of genome stability.
|
| |
Curr Biol, 15,
68-72.
|
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|
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V.N.Uversky,
C.J.Oldfield,
and
A.K.Dunker
(2005).
Showing your ID: intrinsic disorder as an ID for recognition, regulation and cell signaling.
|
| |
J Mol Recognit, 18,
343-384.
|
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Y.Dai,
B.Wong,
Y.M.Yen,
M.A.Oettinger,
J.Kwon,
and
R.C.Johnson
(2005).
Determinants of HMGB proteins required to promote RAG1/2-recombination signal sequence complex assembly and catalysis during V(D)J recombination.
|
| |
Mol Cell Biol, 25,
4413-4425.
|
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E.Kamau,
K.T.Bauerle,
and
A.Grove
(2004).
The Saccharomyces cerevisiae high mobility group box protein HMO1 contains two functional DNA binding domains.
|
| |
J Biol Chem, 279,
55234-55240.
|
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|
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S.Shivaswamy,
G.A.Kassavetis,
and
P.Bhargava
(2004).
High-level activation of transcription of the yeast U6 snRNA gene in chromatin by the basal RNA polymerase III transcription factor TFIIIC.
|
| |
Mol Cell Biol, 24,
3596-3606.
|
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|
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C.L.Li,
L.I.Hor,
Z.F.Chang,
L.C.Tsai,
W.Z.Yang,
and
H.S.Yuan
(2003).
DNA binding and cleavage by the periplasmic nuclease Vvn: a novel structure with a known active site.
|
| |
EMBO J, 22,
4014-4025.
|
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PDB codes:
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E.O'Flaherty,
and
J.Kaye
(2003).
TOX defines a conserved subfamily of HMG-box proteins.
|
| |
BMC Genomics, 4,
13.
|
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|
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H.Szerlong,
A.Saha,
and
B.R.Cairns
(2003).
The nuclear actin-related proteins Arp7 and Arp9: a dimeric module that cooperates with architectural proteins for chromatin remodeling.
|
| |
EMBO J, 22,
3175-3187.
|
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|
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J.Klass,
F.V.Murphy,
S.Fouts,
M.Serenil,
A.Changela,
J.Siple,
and
M.E.Churchill
(2003).
The role of intercalating residues in chromosomal high-mobility-group protein DNA binding, bending and specificity.
|
| |
Nucleic Acids Res, 31,
2852-2864.
|
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S.Ruone,
A.R.Rhoades,
and
T.Formosa
(2003).
Multiple Nhp6 molecules are required to recruit Spt16-Pob3 to form yFACT complexes and to reorganize nucleosomes.
|
| |
J Biol Chem, 278,
45288-45295.
|
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E.Kanaya,
N.Nakajima,
and
K.Okada
(2002).
Non-sequence-specific DNA binding by the FILAMENTOUS FLOWER protein from Arabidopsis thaliana is reduced by EDTA.
|
| |
J Biol Chem, 277,
11957-11964.
|
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|
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K.Mitsouras,
B.Wong,
C.Arayata,
R.C.Johnson,
and
M.Carey
(2002).
The DNA architectural protein HMGB1 displays two distinct modes of action that promote enhanceosome assembly.
|
| |
Mol Cell Biol, 22,
4390-4401.
|
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|
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U.Narendra,
L.Zhu,
B.Li,
J.Wilken,
and
M.A.Weiss
(2002).
Sex-specific gene regulation. The Doublesex DM motif is a bipartite DNA-binding domain.
|
| |
J Biol Chem, 277,
43463-43473.
|
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X.Lv,
D.D.Xu,
D.P.Liu,
L.Li,
D.L.Hao,
and
C.C.Liang
(2002).
High-mobility group protein 2 may be involved in the locus control region regulation of the beta-globin gene cluster.
|
| |
Biochem Cell Biol, 80,
765-770.
|
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J.O.Thomas,
and
A.A.Travers
(2001).
HMG1 and 2, and related 'architectural' DNA-binding proteins.
|
| |
Trends Biochem Sci, 26,
167-174.
|
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M.Kruppa,
R.D.Moir,
D.Kolodrubetz,
and
I.M.Willis
(2001).
Nhp6, an HMG1 protein, functions in SNR6 transcription by RNA polymerase III in S. cerevisiae.
|
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Mol Cell, 7,
309-318.
|
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M.Stros
(2001).
Two mutations of basic residues within the N-terminus of HMG-1 B domain with different effects on DNA supercoiling and binding to bent DNA.
|
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Biochemistry, 40,
4769-4779.
|
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N.K.Brewster,
G.C.Johnston,
and
R.A.Singer
(2001).
A bipartite yeast SSRP1 analog comprised of Pob3 and Nhp6 proteins modulates transcription.
|
| |
Mol Cell Biol, 21,
3491-3502.
|
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P.D.Cary,
C.M.Read,
B.Davis,
P.C.Driscoll,
and
C.Crane-Robinson
(2001).
Solution structure and backbone dynamics of the DNA-binding domain of mouse Sox-5.
|
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Protein Sci, 10,
83-98.
|
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PDB code:
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R.Cerdan,
D.Payet,
J.C.Yang,
A.A.Travers,
and
D.Neuhaus
(2001).
HMG-D complexed to a bulge DNA: an NMR model.
|
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Protein Sci, 10,
504-518.
|
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PDB code:
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V.Y.Stefanovsky,
G.Pelletier,
D.P.Bazett-Jones,
C.Crane-Robinson,
and
T.Moss
(2001).
DNA looping in the RNA polymerase I enhancesome is the result of non-cooperative in-phase bending by two UBF molecules.
|
| |
Nucleic Acids Res, 29,
3241-3247.
|
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Y.M.Yen,
P.M.Roberts,
and
R.C.Johnson
(2001).
Nuclear localization of the Saccharomyces cerevisiae HMG protein NHP6A occurs by a Ran-independent nonclassical pathway.
|
| |
Traffic, 2,
449-464.
|
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A.Travers
(2000).
Recognition of distorted DNA structures by HMG domains.
|
| |
Curr Opin Struct Biol, 10,
102-109.
|
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C.I.Webster,
M.A.Cooper,
L.C.Packman,
D.H.Williams,
and
J.C.Gray
(2000).
Kinetic analysis of high-mobility-group proteins HMG-1 and HMG-I/Y binding to cholesterol-tagged DNA on a supported lipid monolayer.
|
| |
Nucleic Acids Res, 28,
1618-1624.
|
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|
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E.R.Jamieson,
and
S.J.Lippard
(2000).
Stopped-flow fluorescence studies of HMG-domain protein binding to cisplatin-modified DNA.
|
| |
Biochemistry, 39,
8426-8438.
|
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|
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F.V.Murphy,
and
M.E.Churchill
(2000).
Nonsequence-specific DNA recognition: a structural perspective.
|
| |
Structure, 8,
R83-R89.
|
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H.Xin,
S.Taudte,
N.R.Kallenbach,
M.P.Limbach,
and
R.S.Zitomer
(2000).
DNA binding by single HMG box model proteins.
|
| |
Nucleic Acids Res, 28,
4044-4050.
|
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|
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K.B.Ellwood,
Y.M.Yen,
R.C.Johnson,
and
M.Carey
(2000).
Mechanism for specificity by HMG-1 in enhanceosome assembly.
|
| |
Mol Cell Biol, 20,
4359-4370.
|
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|
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K.Röttgers,
N.M.Krohn,
J.Lichota,
C.Stemmer,
T.Merkle,
and
K.D.Grasser
(2000).
DNA-interactions and nuclear localisation of the chromosomal HMG domain protein SSRP1 from maize.
|
| |
Plant J, 23,
395-405.
|
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|
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L.K.Dow,
D.N.Jones,
S.A.Wolfe,
G.L.Verdine,
and
M.E.Churchill
(2000).
Structural studies of the high mobility group globular domain and basic tail of HMG-D bound to disulfide cross-linked DNA.
|
| |
Biochemistry, 39,
9725-9736.
|
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L.Tang,
J.Li,
D.S.Katz,
and
J.A.Feng
(2000).
Determining the DNA bending angle induced by non-specific high mobility group-1 (HMG-1) proteins: a novel method.
|
| |
Biochemistry, 39,
3052-3060.
|
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Q.He,
U.M.Ohndorf,
and
S.J.Lippard
(2000).
Intercalating residues determine the mode of HMG1 domains A and B binding to cisplatin-modified DNA.
|
| |
Biochemistry, 39,
14426-14435.
|
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|
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R.S.Watnick,
S.C.Herring,
A.G.Palmer,
and
M.E.Gottesman
(2000).
The carboxyl terminus of phage HK022 Nun includes a novel zinc-binding motif and a tryptophan required for transcription termination.
|
| |
Genes Dev, 14,
731-739.
|
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|
|
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|
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F.V.Murphy,
R.M.Sweet,
and
M.E.Churchill
(1999).
The structure of a chromosomal high mobility group protein-DNA complex reveals sequence-neutral mechanisms important for non-sequence-specific DNA recognition.
|
| |
EMBO J, 18,
6610-6618.
|
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PDB code:
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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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