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PDBsum entry 1rfa
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Serine/threonine-protein kinase
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PDB id
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1rfa
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Contents |
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* Residue conservation analysis
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PDB id:
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Serine/threonine-protein kinase
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Title:
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Nmr solution structure of the ras-binding domain of c-raf-1
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Structure:
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Raf1. Chain: a. Fragment: ras binding domain, residues 55 - 132 with an additional ala at the n-terminus. Synonym: raf-rbd, c-raf-1. Engineered: yes
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Source:
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Homo sapiens. Human. Organism_taxid: 9606. Organ: fetal liver. Expressed in: escherichia coli. Expression_system_taxid: 562.
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NMR struc:
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30 models
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Authors:
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S.D.Emerson,V.S.Madison,R.E.Palermo,D.S.Waugh,J.E.Scheffler,K.- L.Tsao,S.E.Kiefer,S.P.Liu,D.C.Fry
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Key ref:
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S.D.Emerson
et al.
(1995).
Solution structure of the Ras-binding domain of c-Raf-1 and identification of its Ras interaction surface.
Biochemistry,
34,
6911-6918.
PubMed id:
DOI:
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Date:
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26-Apr-95
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Release date:
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20-Jun-96
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PROCHECK
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Headers
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References
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P04049
(RAF1_HUMAN) -
RAF proto-oncogene serine/threonine-protein kinase from Homo sapiens
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Seq:
Struc:
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648 a.a.
78 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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Enzyme class:
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E.C.2.7.11.1
- non-specific serine/threonine protein kinase.
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Reaction:
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1.
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L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + H+
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2.
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L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] + ADP + H+
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L-seryl-[protein]
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+
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ATP
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=
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O-phospho-L-seryl-[protein]
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+
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ADP
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+
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H(+)
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L-threonyl-[protein]
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+
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ATP
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=
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O-phospho-L-threonyl-[protein]
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+
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ADP
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+
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H(+)
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Molecule diagrams generated from .mol files obtained from the
KEGG ftp site
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DOI no:
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Biochemistry
34:6911-6918
(1995)
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PubMed id:
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Solution structure of the Ras-binding domain of c-Raf-1 and identification of its Ras interaction surface.
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S.D.Emerson,
V.S.Madison,
R.E.Palermo,
D.S.Waugh,
J.E.Scheffler,
K.L.Tsao,
S.E.Kiefer,
S.P.Liu,
D.C.Fry.
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ABSTRACT
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The structure of the Ras-binding domain of human c-Raf-1 (residues 55-132) has
been determined in solution by nuclear magnetic resonance (NMR) spectroscopy.
Following complete assignment of the backbone and side-chain 1H, 15N, and 13C
resonances, the structure was calculated using the program CHARMM. Over 1300
NOE-derived constraints were applied, resulting in a detailed structure. The
fold of Raf55-132 consists of a five-stranded beta-sheet, a 12-residue
alpha-helix, and an additional one-turn helix. It is similar to those of
ubiquitin and the IgG-binding domain of protein G, although the three proteins
share very little sequence identity. The surface of Raf55-132 that interacts
with Ras has been identified by monitoring perturbation of line widths and
chemical shifts of 15N-labeled Raf55-132 resonances during titration with
unlabeled Ras-GMPPNP. The Ras-binding site is contained within a spatially
contiguous patch comprised of the N-terminal beta-hairpin and the C-terminal end
of the alpha-helix.
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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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C.Kiel,
D.Filchtinski,
M.Spoerner,
G.Schreiber,
H.R.Kalbitzer,
and
C.Herrmann
(2009).
Improved binding of raf to Ras.GDP is correlated with biological activity.
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J Biol Chem,
284,
31893-31902.
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G.Fuentes,
and
A.Valencia
(2009).
Ras classical effectors: new tales from in silico complexes.
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Trends Biochem Sci,
34,
533-539.
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C.Kiel,
D.Aydin,
and
L.Serrano
(2008).
Association rate constants of ras-effector interactions are evolutionarily conserved.
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PLoS Comput Biol,
4,
e1000245.
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K.Furihata,
S.Shimotakahara,
and
M.Tashiro
(2008).
An efficient use of the WATERGATE W5 sequence for observing a ligand binding with a protein receptor.
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Magn Reson Chem,
46,
799-802.
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L.E.Goldfinger
(2008).
Choose your own path: specificity in Ras GTPase signaling.
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Mol Biosyst,
4,
293-299.
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D.O.Cicero,
G.M.Contessa,
T.A.Pertinhez,
M.Gallo,
A.M.Katsuyama,
M.Paci,
C.S.Farah,
and
A.Spisni
(2007).
Solution structure of ApaG from Xanthomonas axonopodis pv. citri reveals a fibronectin-3 fold.
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Proteins,
67,
490-500.
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PDB code:
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D.T.Leicht,
V.Balan,
A.Kaplun,
V.Singh-Gupta,
L.Kaplun,
M.Dobson,
and
G.Tzivion
(2007).
Raf kinases: function, regulation and role in human cancer.
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Biochim Biophys Acta,
1773,
1196-1212.
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E.Hwang,
K.S.Ryu,
K.Pääkkönen,
P.Güntert,
H.K.Cheong,
D.S.Lim,
J.O.Lee,
Y.H.Jeon,
and
C.Cheong
(2007).
Structural insight into dimeric interaction of the SARAH domains from Mst1 and RASSF family proteins in the apoptosis pathway.
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Proc Natl Acad Sci U S A,
104,
9236-9241.
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PDB code:
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S.Tomić,
B.Bertosa,
T.Wang,
and
R.C.Wade
(2007).
COMBINE analysis of the specificity of binding of Ras proteins to their effectors.
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Proteins,
67,
435-447.
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M.Kukimoto-Niino,
T.Takagi,
R.Akasaka,
K.Murayama,
T.Uchikubo-Kamo,
T.Terada,
M.Inoue,
S.Watanabe,
A.Tanaka,
Y.Hayashizaki,
T.Kigawa,
M.Shirouzu,
and
S.Yokoyama
(2006).
Crystal structure of the RUN domain of the RAP2-interacting protein x.
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J Biol Chem,
281,
31843-31853.
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PDB codes:
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D.C.Fry,
and
L.T.Vassilev
(2005).
Targeting protein-protein interactions for cancer therapy.
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J Mol Med,
83,
955-963.
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F.X.Campbell-Valois,
K.Tarassov,
and
S.W.Michnick
(2005).
Massive sequence perturbation of a small protein.
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Proc Natl Acad Sci U S A,
102,
14988-14993.
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S.Shimotakahara,
K.Furihata,
and
M.Tashiro
(2005).
Application of NMR screening techniques for observing ligand binding with a protein receptor.
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Magn Reson Chem,
43,
69-72.
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E.J.Helmreich
(2004).
Structural flexibility of small GTPases. Can it explain their functional versatility?
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Biol Chem,
385,
1121-1136.
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H.Gohlke,
and
D.A.Case
(2004).
Converging free energy estimates: MM-PB(GB)SA studies on the protein-protein complex Ras-Raf.
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J Comput Chem,
25,
238-250.
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H.Gohlke,
L.A.Kuhn,
and
D.A.Case
(2004).
Change in protein flexibility upon complex formation: analysis of Ras-Raf using molecular dynamics and a molecular framework approach.
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Proteins,
56,
322-337.
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D.Owen,
P.N.Lowe,
D.Nietlispach,
C.E.Brosnan,
D.Y.Chirgadze,
P.J.Parker,
T.L.Blundell,
and
H.R.Mott
(2003).
Molecular dissection of the interaction between the small G proteins Rac1 and RhoA and protein kinase C-related kinase 1 (PRK1).
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J Biol Chem,
278,
50578-50587.
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PDB code:
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H.Utsumi,
H.Seki,
K.Yamaguchi,
and
M.Tashiro
(2003).
Segment identification of a ligand binding with a protein receptor using multidimensional T1rho-, diffusion-filtered and diffusion-ordered NOESY experiments.
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Anal Sci,
19,
1441-1443.
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J.Ash,
C.Wu,
R.Larocque,
M.Jamal,
W.Stevens,
M.Osborne,
D.Y.Thomas,
and
M.Whiteway
(2003).
Genetic analysis of the interface between Cdc42p and the CRIB domain of Ste20p in Saccharomyces cerevisiae.
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Genetics,
163,
9.
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S.D.Emerson,
R.Palermo,
C.M.Liu,
J.W.Tilley,
L.Chen,
W.Danho,
V.S.Madison,
D.N.Greeley,
G.Ju,
and
D.C.Fry
(2003).
NMR characterization of interleukin-2 in complexes with the IL-2Ralpha receptor component, and with low molecular weight compounds that inhibit the IL-2/IL-Ralpha interaction.
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Protein Sci,
12,
811-822.
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G.G.Kelley,
S.E.Reks,
J.M.Ondrako,
and
A.V.Smrcka
(2001).
Phospholipase C(epsilon): a novel Ras effector.
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EMBO J,
20,
743-754.
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K.Scheffzek,
P.Grünewald,
S.Wohlgemuth,
W.Kabsch,
H.Tu,
M.Wigler,
A.Wittinghofer,
and
C.Herrmann
(2001).
The Ras-Byr2RBD complex: structural basis for Ras effector recognition in yeast.
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Structure,
9,
1043-1050.
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PDB code:
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W.Gronwald,
F.Huber,
P.Grünewald,
M.Spörner,
S.Wohlgemuth,
C.Herrmann,
and
H.R.Kalbitzer
(2001).
Solution structure of the Ras binding domain of the protein kinase Byr2 from Schizosaccharomyces pombe.
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Structure,
9,
1029-1041.
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PDB code:
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D.Owen,
H.R.Mott,
E.D.Laue,
and
P.N.Lowe
(2000).
Residues in Cdc42 that specify binding to individual CRIB effector proteins.
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Biochemistry,
39,
1243-1250.
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J.L.Baber,
D.Levens,
D.Libutti,
and
N.Tjandra
(2000).
Chemical shift mapped DNA-binding sites and 15N relaxation analysis of the C-terminal KH domain of heterogeneous nuclear ribonucleoprotein K.
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Biochemistry,
39,
6022-6032.
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A.M.Wyndham,
R.T.Baker,
and
G.Chelvanayagam
(1999).
The Ubp6 family of deubiquitinating enzymes contains a ubiquitin-like domain: SUb.
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Protein Sci,
8,
1268-1275.
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B.Bauer,
G.Mirey,
I.R.Vetter,
J.A.García-Ranea,
A.Valencia,
A.Wittinghofer,
J.H.Camonis,
and
R.H.Cool
(1999).
Effector recognition by the small GTP-binding proteins Ras and Ral.
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J Biol Chem,
274,
17763-17770.
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J.Zeng,
M.Fridman,
H.Maruta,
H.R.Treutlein,
and
T.Simonson
(1999).
Protein-protein recognition: an experimental and computational study of the R89K mutation in Raf and its effect on Ras binding.
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Protein Sci,
8,
50-64.
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M.Shirouzu,
K.Hashimoto,
A.Kikuchi,
and
S.Yokoyama
(1999).
Double-mutant analysis of the interaction of Ras with the Ras-binding domain of RGL.
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Biochemistry,
38,
5103-5110.
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R.Maesaki,
K.Ihara,
T.Shimizu,
S.Kuroda,
K.Kaibuchi,
and
T.Hakoshima
(1999).
The structural basis of Rho effector recognition revealed by the crystal structure of human RhoA complexed with the effector domain of PKN/PRK1.
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Mol Cell,
4,
793-803.
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PDB code:
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D.Esser,
B.Bauer,
R.M.Wolthuis,
A.Wittinghofer,
R.H.Cool,
and
P.Bayer
(1998).
Structure determination of the Ras-binding domain of the Ral-specific guanine nucleotide exchange factor Rlf.
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Biochemistry,
37,
13453-13462.
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PDB code:
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J.B.Pracyk,
K.Tanaka,
D.D.Hegland,
K.S.Kim,
R.Sethi,
I.I.Rovira,
D.R.Blazina,
L.Lee,
J.T.Bruder,
I.Kovesdi,
P.J.Goldshmidt-Clermont,
K.Irani,
and
T.Finkel
(1998).
A requirement for the rac1 GTPase in the signal transduction pathway leading to cardiac myocyte hypertrophy.
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J Clin Invest,
102,
929-937.
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M.K.Greene,
K.Maskos,
and
S.J.Landry
(1998).
Role of the J-domain in the cooperation of Hsp40 with Hsp70.
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Proc Natl Acad Sci U S A,
95,
6108-6113.
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N.V.Anantha,
M.Azam,
and
R.D.Sheardy
(1998).
Porphyrin binding to quadrupled T4G4.
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Biochemistry,
37,
2709-2714.
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D.S.Garrett,
Y.J.Seok,
A.Peterkofsky,
G.M.Clore,
and
A.M.Gronenborn
(1997).
Identification by NMR of the binding surface for the histidine-containing phosphocarrier protein HPr on the N-terminal domain of enzyme I of the Escherichia coli phosphotransferase system.
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Biochemistry,
36,
4393-4398.
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J.Ma,
and
M.Karplus
(1997).
Molecular switch in signal transduction: reaction paths of the conformational changes in ras p21.
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Proc Natl Acad Sci U S A,
94,
11905-11910.
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L.Huang,
X.Weng,
F.Hofer,
G.S.Martin,
and
S.H.Kim
(1997).
Three-dimensional structure of the Ras-interacting domain of RalGDS.
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Nat Struct Biol,
4,
609-615.
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PDB code:
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M.Geyer,
and
A.Wittinghofer
(1997).
GEFs, GAPs, GDIs and effectors: taking a closer (3D) look at the regulation of Ras-related GTP-binding proteins.
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Curr Opin Struct Biol,
7,
786-792.
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M.Geyer,
C.Herrmann,
S.Wohlgemuth,
A.Wittinghofer,
and
H.R.Kalbitzer
(1997).
Structure of the Ras-binding domain of RalGEF and implications for Ras binding and signalling.
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Nat Struct Biol,
4,
694-699.
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PDB code:
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S.R.Sprang
(1997).
G protein mechanisms: insights from structural analysis.
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Annu Rev Biochem,
66,
639-678.
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Y.Ito,
K.Yamasaki,
J.Iwahara,
T.Terada,
A.Kamiya,
M.Shirouzu,
Y.Muto,
G.Kawai,
S.Yokoyama,
E.D.Laue,
M.Wälchli,
T.Shibata,
S.Nishimura,
and
T.Miyazawa
(1997).
Regional polysterism in the GTP-bound form of the human c-Ha-Ras protein.
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| |
Biochemistry,
36,
9109-9119.
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PDB code:
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C.Block,
R.Janknecht,
C.Herrmann,
N.Nassar,
and
A.Wittinghofer
(1996).
Quantitative structure-activity analysis correlating Ras/Raf interaction in vitro to Raf activation in vivo.
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| |
Nat Struct Biol,
3,
244-251.
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F.McCormick,
and
A.Wittinghofer
(1996).
Interactions between Ras proteins and their effectors.
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| |
Curr Opin Biotechnol,
7,
449-456.
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H.R.Mott,
J.W.Carpenter,
S.Zhong,
S.Ghosh,
R.M.Bell,
and
S.L.Campbell
(1996).
The solution structure of the Raf-1 cysteine-rich domain: a novel ras and phospholipid binding site.
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| |
Proc Natl Acad Sci U S A,
93,
8312-8317.
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PDB codes:
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M.S.McAlister,
H.R.Mott,
P.A.van der Merwe,
I.D.Campbell,
S.J.Davis,
and
P.C.Driscoll
(1996).
NMR analysis of interacting soluble forms of the cell-cell recognition molecules CD2 and CD48.
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| |
Biochemistry,
35,
5982-5991.
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S.Grzesiek,
S.J.Stahl,
P.T.Wingfield,
and
A.Bax
(1996).
The CD4 determinant for downregulation by HIV-1 Nef directly binds to Nef. Mapping of the Nef binding surface by NMR.
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| |
Biochemistry,
35,
10256-10261.
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B.Bax,
and
H.Jhoti
(1995).
Protein-protein interactions. Putting the pieces together.
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| |
Curr Biol,
5,
1119-1121.
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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
