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Methyltransferase
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PDB id
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1yub
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Contents |
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* Residue conservation analysis
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PDB id:
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Methyltransferase
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Title:
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Solution structure of an rrna methyltransferase (ermam) that confers macrolide-lincosamide-streptogramin antibiotic resistance, nmr, minimized average structure
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Structure:
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Rrna methyltransferase. Chain: a. Synonym: ermam. Engineered: yes. Mutation: yes
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Source:
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Streptococcus pneumoniae. Organism_taxid: 1313. Strain: 5728, a clinical isolate from abbott culture collection. Cell_line: bl21. Gene: erm. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.
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NMR struc:
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1 models
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Authors:
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L.Yu,A.M.Petros,A.Schnuchel,P.Zhong,J.M.Severin,K.Walter, T.F.Holzman,S.W.Fesik
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Key ref:
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L.Yu
et al.
(1997).
Solution structure of an rRNA methyltransferase (ErmAM) that confers macrolide-lincosamide-streptogramin antibiotic resistance.
Nat Struct Biol,
4,
483-489.
PubMed id:
DOI:
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Date:
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04-Mar-97
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Release date:
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04-Mar-98
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PROCHECK
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Headers
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References
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P21236
(ERM_STRPN) -
rRNA adenine N-6-methyltransferase
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Seq:
Struc:
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245 a.a.
245 a.a.*
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Key: |
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PfamA domain |
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Secondary structure |
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CATH domain |
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*
PDB and UniProt seqs differ
at 3 residue positions (black
crosses)
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Enzyme class:
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E.C.2.1.1.184
- 23S rRNA (adenine(2085)-N(6))-dimethyltransferase.
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Reaction:
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2 S-adenosyl-L-methionine + adenine2085 in 23S rRNA = 2 S-adenosyl-L- homocysteine + N6-dimethyladenine2085 in 23S rRNA
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2
×
S-adenosyl-L-methionine
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+
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adenine(2085) in 23S rRNA
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=
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2
×
S-adenosyl-L- homocysteine
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+
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N(6)-dimethyladenine(2085) in 23S rRNA
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Molecule diagrams generated from .mol files obtained from the
KEGG ftp site
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Gene Ontology (GO) functional annotation
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Biological process
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response to antibiotic
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2 terms
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Biochemical function
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transferase activity
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5 terms
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DOI no:
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Nat Struct Biol
4:483-489
(1997)
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PubMed id:
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Solution structure of an rRNA methyltransferase (ErmAM) that confers macrolide-lincosamide-streptogramin antibiotic resistance.
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L.Yu,
A.M.Petros,
A.Schnuchel,
P.Zhong,
J.M.Severin,
K.Walter,
T.F.Holzman,
S.W.Fesik.
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ABSTRACT
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The Erm family of methyltransferases is responsible for the development of
resistance to the macrolide-lincosamide-streptogramin type B (MLS) antibiotics.
These enzymes methylate an adenine of 23S ribosomal RNA that prevents the MLS
antibiotics from binding to the ribosome and exhibiting their antibacterial
activity. Here we describe the three-dimensional structure of an Erm family
member, ErmAM, as determined by NMR spectroscopy. The catalytic domain of ErmAM
is structurally similar to that found in other methyltransferases and consists
of a seven-stranded beta-sheet flanked by alpha-helices and a small two-stranded
beta-sheet. In contrast to the catalytic domain, the substrate binding domain is
different from other methyltransferases and adopts a novel fold that consists of
four alpha-helices.
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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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K.L.Tkaczuk
(2010).
Trm13p, the tRNA:Xm4 modification enzyme from Saccharomyces cerevisiae is a member of the Rossmann-fold MTase superfamily: prediction of structure and active site.
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J Mol Model, 16,
599-606.
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C.Tu,
J.E.Tropea,
B.P.Austin,
D.L.Court,
D.S.Waugh,
and
X.Ji
(2009).
Structural basis for binding of RNA and cofactor by a KsgA methyltransferase.
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Structure, 17,
374-385.
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PDB codes:
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H.C.O'Farrell,
Z.Xu,
G.M.Culver,
and
J.P.Rife
(2008).
Sequence and structural evolution of the KsgA/Dim1 methyltransferase family.
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BMC Res Notes, 1,
108.
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C.T.Madsen,
L.Jakobsen,
K.Buriánková,
F.Doucet-Populaire,
J.L.Pernodet,
and
S.Douthwaite
(2005).
Methyltransferase Erm(37) slips on rRNA to confer atypical resistance in Mycobacterium tuberculosis.
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J Biol Chem, 280,
38942-38947.
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K.L.Constantine,
S.R.Krystek,
M.D.Healy,
M.L.Doyle,
N.O.Siemers,
J.Thanassi,
N.Yan,
D.Xie,
V.Goldfarb,
J.Yanchunas,
L.Tao,
B.A.Dougherty,
and
B.T.Farmer
(2005).
Structural and functional characterization of CFE88: evidence that a conserved and essential bacterial protein is a methyltransferase.
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Protein Sci, 14,
1472-1484.
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V.Tugarinov,
W.Y.Choy,
V.Y.Orekhov,
and
L.E.Kay
(2005).
Solution NMR-derived global fold of a monomeric 82-kDa enzyme.
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Proc Natl Acad Sci U S A, 102,
622-627.
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PDB code:
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W.Sun,
X.Xu,
M.Pavlova,
A.M.Edwards,
A.Joachimiak,
A.Savchenko,
and
D.Christendat
(2005).
The crystal structure of a novel SAM-dependent methyltransferase PH1915 from Pyrococcus horikoshii.
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Protein Sci, 14,
3121-3128.
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PDB code:
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G.Maravić,
J.M.Bujnicki,
and
M.Flögel
(2004).
Mutational analysis of basic residues in the N-terminus of the rRNA:m6A methyltransferase ErmC'.
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Folia Microbiol (Praha), 49,
3-7.
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K.Buriánková,
F.Doucet-Populaire,
O.Dorson,
A.Gondran,
J.C.Ghnassia,
J.Weiser,
and
J.L.Pernodet
(2004).
Molecular basis of intrinsic macrolide resistance in the Mycobacterium tuberculosis complex.
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Antimicrob Agents Chemother, 48,
143-150.
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G.Maravić,
J.M.Bujnicki,
M.Feder,
S.Pongor,
and
M.Flögel
(2003).
Alanine-scanning mutagenesis of the predicted rRNA-binding domain of ErmC' redefines the substrate-binding site and suggests a model for protein-RNA interactions.
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Nucleic Acids Res, 31,
4941-4949.
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H.J.Ahn,
H.W.Kim,
H.J.Yoon,
B.I.Lee,
S.W.Suh,
and
J.K.Yang
(2003).
Crystal structure of tRNA(m1G37)methyltransferase: insights into tRNA recognition.
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EMBO J, 22,
2593-2603.
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PDB codes:
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J.E.Harlan,
D.A.Egan,
U.S.Ladror,
S.Snyder,
M.I.Tang,
A.Buko,
and
T.F.Holzman
(2003).
Driving affinity selection by centrifugal force.
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Assay Drug Dev Technol, 1,
507-519.
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G.Michel,
V.Sauvé,
R.Larocque,
Y.Li,
A.Matte,
and
M.Cygler
(2002).
The structure of the RlmB 23S rRNA methyltransferase reveals a new methyltransferase fold with a unique knot.
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Structure, 10,
1303-1315.
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PDB code:
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K.A.Farrow,
D.Lyras,
G.Polekhina,
K.Koutsis,
M.W.Parker,
and
J.I.Rood
(2002).
Identification of essential residues in the Erm(B) rRNA methyltransferase of Clostridium perfringens.
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Antimicrob Agents Chemother, 46,
1253-1261.
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F.D.Schubot,
C.J.Chen,
J.P.Rose,
T.A.Dailey,
H.A.Dailey,
and
B.C.Wang
(2001).
Crystal structure of the transcription factor sc-mtTFB offers insights into mitochondrial transcription.
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Protein Sci, 10,
1980-1988.
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PDB code:
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X.Cheng,
and
R.J.Roberts
(2001).
AdoMet-dependent methylation, DNA methyltransferases and base flipping.
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Nucleic Acids Res, 29,
3784-3795.
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M.M.Skinner,
J.M.Puvathingal,
R.L.Walter,
and
A.M.Friedman
(2000).
Crystal structure of protein isoaspartyl methyltransferase: a catalyst for protein repair.
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Structure, 8,
1189-1201.
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PDB code:
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N.K.Goto,
and
L.E.Kay
(2000).
New developments in isotope labeling strategies for protein solution NMR spectroscopy.
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Curr Opin Struct Biol, 10,
585-592.
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|
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P.Zhong,
and
V.D.Shortridge
(2000).
The role of efflux in macrolide resistance.
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Drug Resist Updat, 3,
325-329.
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R.B.Giannattasio,
and
B.Weisblum
(2000).
Modulation of erm methyltransferase activity by peptides derived from phage display.
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Antimicrob Agents Chemother, 44,
1961-1963.
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A.K.Nielsen,
S.Douthwaite,
and
B.Vester
(1999).
Negative in vitro selection identifies the rRNA recognition motif for ErmE methyltransferase.
|
| |
RNA, 5,
1034-1041.
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|
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A.Niewmierzycka,
and
S.Clarke
(1999).
S-Adenosylmethionine-dependent methylation in Saccharomyces cerevisiae. Identification of a novel protein arginine methyltransferase.
|
| |
J Biol Chem, 274,
814-824.
|
|
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|
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B.Holz,
N.Dank,
J.E.Eickhoff,
G.Lipps,
G.Krauss,
and
E.Weinhold
(1999).
Identification of the binding site for the extrahelical target base in N6-adenine DNA methyltransferases by photo-cross-linking with duplex oligodeoxyribonucleotides containing 5-iodouracil at the target position.
|
| |
J Biol Chem, 274,
15066-15072.
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H.Pues,
N.Bleimling,
B.Holz,
J.Wölcke,
and
E.Weinhold
(1999).
Functional roles of the conserved aromatic amino acid residues at position 108 (motif IV) and position 196 (motif VIII) in base flipping and catalysis by the N6-adenine DNA methyltransferase from Thermus aquaticus.
|
| |
Biochemistry, 38,
1426-1434.
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L.H.Hansen,
B.Vester,
and
S.Douthwaite
(1999).
Core sequence in the RNA motif recognized by the ErmE methyltransferase revealed by relaxing the fidelity of the enzyme for its target.
|
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RNA, 5,
93.
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R.Reid,
P.J.Greene,
and
D.V.Santi
(1999).
Exposition of a family of RNA m(5)C methyltransferases from searching genomic and proteomic sequences.
|
| |
Nucleic Acids Res, 27,
3138-3145.
|
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A.M.Reeve,
S.D.Breazeale,
and
C.A.Townsend
(1998).
Purification, characterization, and cloning of an S-adenosylmethionine-dependent 3-amino-3-carboxypropyltransferase in nocardicin biosynthesis.
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J Biol Chem, 273,
30695-30703.
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C.Schmutte,
and
P.A.Jones
(1998).
Involvement of DNA methylation in human carcinogenesis.
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Biol Chem, 379,
377-388.
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D.E.Bussiere,
S.W.Muchmore,
C.G.Dealwis,
G.Schluckebier,
V.L.Nienaber,
R.P.Edalji,
K.A.Walter,
U.S.Ladror,
T.F.Holzman,
and
C.Abad-Zapatero
(1998).
Crystal structure of ErmC', an rRNA methyltransferase which mediates antibiotic resistance in bacteria.
|
| |
Biochemistry, 37,
7103-7112.
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PDB code:
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G.M.Clore,
and
A.M.Gronenborn
(1998).
NMR structure determination of proteins and protein complexes larger than 20 kDa.
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Curr Opin Chem Biol, 2,
564-570.
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K.H.Gardner,
and
L.E.Kay
(1998).
The use of 2H, 13C, 15N multidimensional NMR to study the structure and dynamics of proteins.
|
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Annu Rev Biophys Biomol Struct, 27,
357-406.
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P.H.Tran,
Z.R.Korszun,
S.Cerritelli,
S.S.Springhorn,
and
S.A.Lacks
(1998).
Crystal structure of the DpnM DNA adenine methyltransferase from the DpnII restriction system of streptococcus pneumoniae bound to S-adenosylmethionine.
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Structure, 6,
1563-1575.
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PDB code:
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L.E.Kay,
and
K.H.Gardner
(1997).
Solution NMR spectroscopy beyond 25 kDa.
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Curr Opin Struct Biol, 7,
722-731.
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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
