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PDBsum entry 1itf
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References listed in PDB file
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Key reference
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Title
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The three-Dimensional high resolution structure of human interferon alpha-2a determined by heteronuclear nmr spectroscopy in solution.
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Authors
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W.Klaus,
B.Gsell,
A.M.Labhardt,
B.Wipf,
H.Senn.
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Ref.
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J Mol Biol, 1997,
274,
661-675.
[DOI no: ]
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PubMed id
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Note In the PDB file this reference is
annotated as "TO BE PUBLISHED".
The citation details given above were identified by an automated
search of PubMed on title and author
names, giving a
percentage match of
95%.
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Abstract
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The solution structure of recombinant human interferon alpha-2a (Roferon-A) has
been determined by multidimensional heteronuclear NMR spectroscopy. The
calculations using simulated annealing produced a family of 24 convergent
structures which satisfy the experimental restraints comprising 1541 NOE-derived
inter-proton distances, 187 dihedral restraints, 66 pairs of hydrogen bond
restraints, and six upper and lower limits for two disulfide bridges. The
fractional labeling of methyl groups allowed their direct and unambiguous
stereospecific assignment which proved to be essential for obtaining a high
resolution of the structures. A best fit superposition of residues 10 to 47, 50
to 101 and 111 to 157 gives an rms deviation of 0.62 A for the backbone heavy
atoms and 1.39 A for all heavy atoms of these segments. The dominant feature of
the structure is a cluster of five alpha-helices, four of which are arranged to
form a left-handed helix bundle with an up-up-down-down topology and two
over-hand connections. The interpretation of heteronuclear 15N-¿1H¿ NOE data
shows the co-existence of flexible regions within an otherwise rigid framework
of the protein. Four stretches of pronounced flexibility can be located:
Cys1-Ser8, Gly44-Ala50, Ile100-Lys112, and Ser160-Glu165. Among the structurally
related four-helical bundle cytokines, the structure of IFN alpha-2a is most
similar to that of human interferon alpha-2b and murine interferon-beta. From
this structural information and mutagenesis data, areas on the surface of the
protein are identified which seem to be important in receptor interactions.
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Figure 4.
Figure 4. Overlay of the side-chains of the well-defined
amino acids of the final structures together with the
polypeptide backbones (in yellow). The side-chains are colored
according to residue type: Asp, Glu: red; Arg, Lys: dark blue;
Ala, Ile, Leu, Phe, Val: cyan; Pro, Trp: green; Thr, Tyr, Ser:
white. The flexible loops are clustered at the top of the
structures.
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Figure 5.
Figure 5. Overlay of the average NMR conformation of human
interferon α-2a (in orange) and the X-ray structure of murine
interferon-β (in cyan) [Senda et al 1995]. The α-helices are
marked with labels A to E close to their N-terminal end. The
Figure was prepared using the program Ribbons 2.0 [Carson 1991].
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The above figures are
reprinted
by permission from Elsevier:
J Mol Biol
(1997,
274,
661-675)
copyright 1997.
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