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PDBsum entry 1awo
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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 solution structure of abl sh3, And its relationship to sh2 in the sh(32) construct.
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Authors
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Y.Q.Gosser,
J.Zheng,
M.Overduin,
B.J.Mayer,
D.Cowburn.
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Ref.
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Structure, 1995,
3,
1075-1086.
[DOI no: ]
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PubMed id
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Abstract
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BACKGROUND: The Src homology domains, SH3 and SH2, of Abl protein tyrosine
kinase regulate enzymatic activity in vivo. Abl SH3 suppresses kinase activity,
whereas Abl SH2 is required for the transforming activity of the activated form
of Abl. We expect that the solution structures of Abl SH3, Abl SH2 and Abl
SH(32) (a dual domain comprising SH3 and SH2 subdomains) will contribute to a
structural basis for understanding the mechanism of the Abl 'regulatory
apparatus'. RESULTS: We present the solution structure of the free Abl SH3
domain and a structural characterization of the Abl regulatory apparatus, the
SH(32) dual domain. The solution structure of Abl SH3 was determined using
multidimensional double resonance NMR spectroscopy. It consists of two
antiparallel beta sheets packed orthogonally, an arrangement first shown in
spectrin SH3. Compared with the crystal structure of the Abl SH3 complexed with
a natural ligand, there is no significant difference in overall folding pattern.
The structure of the Abl SH(32) dual domain was characterized by NMR
spectroscopy using the 1H and 15N resonance assignment of Abl SH3 and Abl SH2.
On the basis of the high degree of similarity in chemical shifts and
hydrogen/deuterium exchange pattern for the individual domains of SH3 and SH2
compared with those of the SH(32) dual domain, a structural model of the Abl
SH(32) regulatory apparatus is suggested. This model is in good agreement with
the ligand-binding characteristics of Abl SH3, SH2 and SH(32). The binding
constants for isolated SH3 and SH2 domains when binding to natural ligands,
measured by intrinsic fluorescence quenching, do not differ significantly from
the constants of these domains within SH(32). CONCLUSION: The solution
structures of free Abl SH3 and Abl SH2, and the structural model of Abl SH(32),
provide information about the overall topology of these modular domains. The
structural model of Abl SH(32), a monomer, consists of the SH3 and SH2 domains
connected by a flexible linker. Sites of ligand binding for the two subdomains
are independent.
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Figure 2.
Figure 2. Sketch of the antiparallel β sheets, S1 and S2, in
the Abl-SH3 solution structure. The observed long-range NOEs
between strands are indicated by solid lines. Hydrogen bonds
from slowly exchanging amides, supported by interstrand NOEs,
are indicated by dashed lines. Figure 2. Sketch of the
antiparallel β sheets, S1 and S2, in the Abl-SH3 solution
structure. The observed long-range NOEs between strands are
indicated by solid lines. Hydrogen bonds from slowly exchanging
amides, supported by interstrand NOEs, are indicated by dashed
lines.
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Figure 9.
Figure 9. Sequences of Abl SH3, SH2 and SH(32) [1 and 34]. The
elements of secondary structure are labeled as for the
individual SH3 and SH2 domains. Loops and turns are not labeled.
The residues in the linker region are indicated with bold green
letters. Residues in lower case result from the expression
system used. Figure 9. Sequences of Abl SH3, SH2 and SH(32)
[[3]1 and [4]34]. The elements of secondary structure are
labeled as for the individual SH3 and SH2 domains. Loops and
turns are not labeled. The residues in the linker region are
indicated with bold green letters. Residues in lower case result
from the expression system used.
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The above figures are
reprinted
by permission from Cell Press:
Structure
(1995,
3,
1075-1086)
copyright 1995.
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Secondary reference #1
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Title
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Mutagenic analysis of the roles of sh2 and sh3 domains in regulation of the abl tyrosine kinase.
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Authors
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B.J.Mayer,
D.Baltimore.
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Ref.
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Mol Cell Biol, 1994,
14,
2883-2894.
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PubMed id
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Secondary reference #2
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Title
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High-Resolution crystal structures of tyrosine kinase sh3 domains complexed with proline-Rich peptides.
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Authors
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A.Musacchio,
M.Saraste,
M.Wilmanns.
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Ref.
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Nat Struct Biol, 1994,
1,
546-551.
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PubMed id
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Secondary reference #3
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Title
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Identification of a ten-Amino acid proline-Rich sh3 binding site.
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Authors
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R.Ren,
B.J.Mayer,
P.Cicchetti,
D.Baltimore.
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Ref.
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Science, 1993,
259,
1157-1161.
[DOI no: ]
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PubMed id
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Secondary reference #4
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Title
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Crystal structure of the sh3 domain in human fyn; comparison of the three-Dimensional structures of sh3 domains in tyrosine kinases and spectrin.
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Authors
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M.E.Noble,
A.Musacchio,
M.Saraste,
S.A.Courtneidge,
R.K.Wierenga.
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Ref.
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Embo J, 1993,
12,
2617-2624.
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PubMed id
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Secondary reference #5
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Title
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Three-Dimensional solution structure of the src homology 2 domain of c-Abl.
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Authors
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M.Overduin,
C.B.Rios,
B.J.Mayer,
D.Baltimore,
D.Cowburn.
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Ref.
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Cell, 1992,
70,
697-704.
[DOI no: ]
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PubMed id
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Secondary reference #6
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Title
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Crystal structure of a src-Homology 3 (sh3) domain.
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Authors
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A.Musacchio,
M.Noble,
R.Pauptit,
R.Wierenga,
M.Saraste.
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Ref.
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Nature, 1992,
359,
851-855.
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PubMed id
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