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* Residue conservation analysis
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PDB id:
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Cytokine
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Title:
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Crystal structure of human interleukin-2 y31c covalently modified at c31 with 3-mercapto-1-(1,3,4,9-tetrahydro-b- carbolin-2-yl)-propan-1-one
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Structure:
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Interleukin-2. Chain: a. Synonym: il-2, t-cell growth factor, tcgf, aldesleukin. Engineered: yes. Mutation: yes
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Source:
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Homo sapiens. Human. Organism_taxid: 9606. Gene: il2. Expressed in: escherichia coli bl21. Expression_system_taxid: 511693.
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Resolution:
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2.20Å
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R-factor:
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0.230
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R-free:
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0.277
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Authors:
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J.Hyde,A.C.Braisted,M.Randal,M.R.Arkin
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Key ref:
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J.Hyde
et al.
(2003).
Discovery and characterization of cooperative ligand binding in the adaptive region of interleukin-2.
Biochemistry,
42,
6475-6483.
PubMed id:
DOI:
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Date:
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03-Dec-02
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Release date:
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18-Dec-02
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PROCHECK
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Headers
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References
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P60568
(IL2_HUMAN) -
Interleukin-2
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Seq:
Struc:
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153 a.a.
121 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 1 residue position (black
cross)
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Gene Ontology (GO) functional annotation
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Cellular component
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extracellular region
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2 terms
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Biological process
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immune response
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27 terms
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Biochemical function
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protein binding
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8 terms
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DOI no:
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Biochemistry
42:6475-6483
(2003)
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PubMed id:
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Discovery and characterization of cooperative ligand binding in the adaptive region of interleukin-2.
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J.Hyde,
A.C.Braisted,
M.Randal,
M.R.Arkin.
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ABSTRACT
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The cytokine hormone interleukin-2 (IL-2) contains a highly adaptive region that
binds small, druglike molecules. The binding properties of this adaptive region
have been explored using a "tethering" method that relies on the
formation of a disulfide bond between the protein and small-molecule ligands.
Using tethering, surface plasmon resonance (SPR), and X-ray crystallography, we
have discovered that the IL-2 adaptive region contains at least two cooperative
binding sites where the binding of a first ligand to one site promotes or
antagonizes the binding of a second ligand to the second site. Cooperative
energies of interaction of -2 kcal/mol are observed. The observation that the
adaptive region contains two adjacent sites may lead to the development of
tight-binding antagonists of a protein-protein interaction. Cooperative ligand
binding in the adaptive region of IL-2 underscores the importance of protein
dynamics in molecular recognition. The tethering approach provides a novel and
general strategy for discovering such cooperative binding interactions in
specific, flexible regions of protein structure.
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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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G.Tóth,
K.Mukhyala,
and
J.A.Wells
(2007).
Computational approach to site-directed ligand discovery.
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Proteins, 68,
551-560.
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C.D.Thanos,
W.L.DeLano,
and
J.A.Wells
(2006).
Hot-spot mimicry of a cytokine receptor by a small molecule.
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Proc Natl Acad Sci U S A, 103,
15422-15427.
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E.R.Zartler,
and
M.J.Shapiro
(2005).
Fragonomics: fragment-based drug discovery.
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Curr Opin Chem Biol, 9,
366-370.
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R.L.Rich,
and
D.G.Myszka
(2005).
Survey of the year 2003 commercial optical biosensor literature.
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J Mol Recognit, 18,
1.
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T.O'Brien,
B.T.Fahr,
M.M.Sopko,
J.W.Lam,
N.D.Waal,
B.C.Raimundo,
H.E.Purkey,
P.Pham,
and
M.J.Romanowski
(2005).
Structural analysis of caspase-1 inhibitors derived from Tethering.
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Acta Crystallogr Sect F Struct Biol Cryst Commun, 61,
451-458.
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PDB codes:
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D.A.Erlanson,
J.A.Wells,
and
A.C.Braisted
(2004).
Tethering: fragment-based drug discovery.
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Annu Rev Biophys Biomol Struct, 33,
199-223.
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D.A.Erlanson,
and
S.K.Hansen
(2004).
Making drugs on proteins: site-directed ligand discovery for fragment-based lead assembly.
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Curr Opin Chem Biol, 8,
399-406.
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I.W.Wainer
(2004).
Finding time for allosteric interactions.
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Nat Biotechnol, 22,
1376-1377.
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M.R.Arkin,
and
J.A.Wells
(2004).
Small-molecule inhibitors of protein-protein interactions: progressing towards the dream.
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Nat Rev Drug Discov, 3,
301-317.
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T.Berg
(2004).
Use of "tethering" for the identification of a small molecule that binds to a dynamic hot spot on the interleukin-2 surface.
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Chembiochem, 5,
1051-1053.
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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
