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* Residue conservation analysis
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DOI no:
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Science
273:464-471
(1996)
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PubMed id:
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Functional mimicry of a protein hormone by a peptide agonist: the EPO receptor complex at 2.8 A.
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O.Livnah,
E.A.Stura,
D.L.Johnson,
S.A.Middleton,
L.S.Mulcahy,
N.C.Wrighton,
W.J.Dower,
L.K.Jolliffe,
I.A.Wilson.
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ABSTRACT
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The functional mimicry of a protein by an unrelated small molecule has been a
formidable challenge. Now, however, the biological activity of a 166-residue
hematopoietic growth hormone, erythropoietin (EPO), with its class 1 cytokine
receptor has been mimicked by a 20-residue cyclic peptide unrelated in sequence
to the natural ligand. The crystal structure at 2.8 A resolution of a complex of
this agonist peptide with the extracellular domain of EPO receptor reveals that
a peptide dimer induces an almost perfect twofold dimerization of the receptor.
The dimer assembly differs from that of the human growth hormone (hGH) receptor
complex and suggests that more than one mode of dimerization may be able to
induce signal transduction and cell proliferation. The EPO receptor binding
site, defined by peptide interaction, corresponds to the smaller functional
epitope identified for hGH receptor. Similarly, the EPO mimetic peptide ligand
can be considered as a minimal hormone, and suggests the design of nonpeptidic
small molecule mimetics for EPO and other cytokines may indeed be achievable.
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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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PDB codes:
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PDB codes:
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CNTO 530 functions as a potent EPO mimetic via unique sustained effects on bone marrow proerythroblast pools.
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Structural organization of a full-length gp130/LIF-R cytokine receptor transmembrane complex.
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Mol Cell,
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PDB code:
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J.A.Robinson,
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A ligand peptide motif selected from a cancer patient is a receptor-interacting site within human interleukin-11.
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PLoS ONE,
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Nature,
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U.Das,
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P.Manral,
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M.Ganguli,
A.K.Verma,
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P.Kaur,
T.P.Singh,
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Hot-spot mimicry of a cytokine receptor by a small molecule.
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Proc Natl Acad Sci U S A,
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PDB code:
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D.J.Stauber,
E.W.Debler,
P.A.Horton,
K.A.Smith,
and
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Crystal structure of the IL-2 signaling complex: paradigm for a heterotrimeric cytokine receptor.
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Proc Natl Acad Sci U S A,
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PDB code:
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J.L.Casey,
A.M.Coley,
G.Street,
K.Parisi,
P.L.Devine,
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Peptide mimotopes selected from a random peptide library for diagnosis of Epstein-Barr virus infection.
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J Clin Microbiol,
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Signals for stress erythropoiesis are integrated via an erythropoietin receptor-phosphotyrosine-343-Stat5 axis.
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J Clin Invest,
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Structure-based design of an agonistic peptide targeting Fas.
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Apoptosis,
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D.Cournoyer,
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Designing scaffolds of peptides for phage display libraries.
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Bow to your partner for signaling.
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Selective complexation of N-alkylpyridinium salts: binding of NAD+ in water.
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Structure-function studies of the functional and binding epitope of the human 37 kDa laminin receptor precursor protein.
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Toward small-molecule agonists of TNF receptors.
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Functional expression of single-chain heterodimeric G-protein-coupled receptors for adenosine and dopamine.
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High thermal stability imparted by a designed tandem Arg-Trp stretch in an alpha-helical coiled coil.
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Genomic drug discovery for apoptosis regulation using a new computer screening amino acid complement wave method.
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Proc Natl Acad Sci U S A,
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PDB code:
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M.J.Boulanger,
A.J.Bankovich,
T.Kortemme,
D.Baker,
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Mol Cell,
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PDB code:
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M.Kawahara,
H.Ueda,
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Proc Natl Acad Sci U S A,
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PDB codes:
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N.Seubert,
Y.Royer,
J.Staerk,
K.F.Kubatzky,
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S.D.Emerson,
R.Palermo,
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L.Chen,
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Protein Sci,
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S.Lien,
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Trends Biotechnol,
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K.Deshayes
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Chembiochem,
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B.E.Willcox,
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A.P.Heikema,
A.P.West,
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(2002).
Crystal structure of LIR-2 (ILT4) at 1.8 A: differences from LIR-1 (ILT2) in regions implicated in the binding of the Human Cytomegalovirus class I MHC homolog UL18.
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BMC Struct Biol,
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PDB code:
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D.I.Zheleva,
C.McInnes,
A.L.Gavine,
N.Z.Zhelev,
P.M.Fischer,
and
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Highly potent p21(WAF1)-derived peptide inhibitors of CDK-mediated pRb phosphorylation: delineation and structural insight into their interactions with cyclin A.
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J Pept Res,
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H.Schooltink,
and
S.Rose-John
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Cytokines as therapeutic drugs.
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J Interferon Cytokine Res,
22,
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J.L.Zhang,
M.Buehner,
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Functional epitope of common gamma chain for interleukin-4 binding.
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Eur J Biochem,
269,
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J.M.Alexander,
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V.van Berkel,
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H.W.Virgin,
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(2002).
Structural basis of chemokine sequestration by a herpesvirus decoy receptor.
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Cell,
111,
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PDB codes:
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K.Tan,
M.Duquette,
J.H.Liu,
Y.Dong,
R.Zhang,
A.Joachimiak,
J.Lawler,
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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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