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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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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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J Mol Biol
247:979-994
(1995)
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PubMed id:
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The solution structure of the F42A mutant of human interleukin 2.
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H.R.Mott,
B.S.Baines,
R.M.Hall,
R.M.Cooke,
P.C.Driscoll,
M.P.Weir,
I.D.Campbell.
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ABSTRACT
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Interleukin 2 (IL-2) is one of the major cytokines produced by T lymphocytes in
response to antigen. It is a potent growth and differentiation factor for
several cell-types and is structurally related to the four-helix bundle family
of cytokines. Mutation of residue Phe42 to Ala abolishes binding to the alpha
chain of the tri-partite IL-2 receptor. The three-dimensional structure of the
F42A mutant IL-2 has been calculated by two dimensional NMR methods and compared
to a structure of wild-type IL-2 determined by X-ray crystallography. The
overall topology of the two structures is the same. The main differences between
the structures are within the ill-defined loops connecting the helices and the
region of the protein that is believed to interact with the alpha-chain of the
receptor. Thus, the mutation of Phe42 to Ala does not perturb the overall
three-dimensional structure of IL-2, and does not appear to change the putative
binding sites for the beta and gamma chains of the receptor. The structural
differences observed in this mutant suggest that the replacement of Phe42 with
Ala causes the re-orientation of neighbouring side-chains that are also involved
in binding the alpha-chain of the receptor.
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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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A.Fontana,
B.Spolaore,
A.Mero,
and
F.M.Veronese
(2008).
Site-specific modification and PEGylation of pharmaceutical proteins mediated by transglutaminase.
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Adv Drug Deliv Rev, 60,
13-28.
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K.Bondensgaard,
J.Breinholt,
D.Madsen,
D.H.Omkvist,
L.Kang,
A.Worsaae,
P.Becker,
C.B.Schiødt,
and
S.A.Hjorth
(2007).
The existence of multiple conformers of interleukin-21 directs engineering of a superpotent analogue.
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J Biol Chem, 282,
23326-23336.
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PDB code:
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D.C.Fry
(2006).
Protein-protein interactions as targets for small molecule drug discovery.
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Biopolymers, 84,
535-552.
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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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M.R.Arkin,
M.Randal,
W.L.DeLano,
J.Hyde,
T.N.Luong,
J.D.Oslob,
D.R.Raphael,
L.Taylor,
J.Wang,
R.S.McDowell,
J.A.Wells,
and
A.C.Braisted
(2003).
Binding of small molecules to an adaptive protein-protein interface.
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Proc Natl Acad Sci U S A, 100,
1603-1608.
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PDB codes:
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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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H.Sato
(2002).
Enzymatic procedure for site-specific pegylation of proteins.
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Adv Drug Deliv Rev, 54,
487-504.
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M.D.Lanigan,
J.E.Tudor,
M.W.Pennington,
and
R.S.Norton
(2001).
A helical capping motif in ShK toxin and its role in helix stabilization.
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Biopolymers, 58,
422-436.
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P.V.Afonin,
A.V.Fokin,
I.N.Tsygannik,
I.Y.Mikhailova,
L.V.Onoprienko,
I.I.Mikhaleva,
V.T.Ivanov,
T.Y.Mareeva,
V.A.Nesmeyanov,
N.Li,
W.A.Pangborn,
W.L.Duax,
and
V.Z.Pletnev
(2001).
Crystal structure of an anti-interleukin-2 monoclonal antibody Fab complexed with an antigenic nonapeptide.
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Protein Sci, 10,
1514-1521.
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PDB code:
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S.Endo,
Y.Yamamoto,
T.Sugawara,
O.Nishimura,
and
M.Fujino
(2001).
The additional methionine residue at the N-terminus of bacterially expressed human interleukin-2 affects the interaction between the N- and C-termini.
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Biochemistry, 40,
914-919.
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R.J.Simpson,
A.Hammacher,
D.K.Smith,
J.M.Matthews,
and
L.D.Ward
(1997).
Interleukin-6: structure-function relationships.
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Protein Sci, 6,
929-955.
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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
