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PDBsum entry 1mwp
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Sugar binding protein
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PDB id
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1mwp
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Contents |
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* Residue conservation analysis
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References listed in PDB file
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Key reference
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Title
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Crystal structure of the n-Terminal, Growth factor-Like domain of alzheimer amyloid precursor protein.
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Authors
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J.Rossjohn,
R.Cappai,
S.C.Feil,
A.Henry,
W.J.Mckinstry,
D.Galatis,
L.Hesse,
G.Multhaup,
K.Beyreuther,
C.L.Masters,
M.W.Parker.
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Ref.
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Nat Struct Biol, 1999,
6,
327-331.
[DOI no: ]
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PubMed id
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Abstract
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Amyloid precursor protein (APP) plays a central role in Alzheimer disease. A
proteolytic-breakdown product of APP, called beta-amyloid, is a major component
of the diffuse and fibrillar deposits found in Alzheimer diseased brains. The
normal physiological role of APP remains largely unknown despite much work. A
knowledge of its function will not only provide insights into the genesis of the
disease but may also prove vital in the development of an effective therapy.
Here we describe the 1.8 A resolution crystal structure of the N-terminal,
heparin-binding domain of APP (residues 28-123), which is responsible, among
other things, for stimulation of neurite outgrowth. The structure reveals a
highly charged basic surface that may interact with glycosaminoglycans in the
brain and an abutting hydrophobic surface that is proposed to play an important
functional role such as dimerization or ligand binding. Structural similarities
with cysteine-rich growth factors, taken together with its known
growth-promoting properties, suggests the APP N-terminal domain could function
as a growth factor in vivo.
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Figure 1.
Figure 1. Structure of the APP N-terminal domain. a, A ribbon
diagram indicating the location of secondary structure. Sheet A
is colored blue, sheet B is in orange and sheet C is shown in
brown. The disulfide bridges are shown in ball-and-stick, and
the tip of the  -hairpin
loop is indicated. This figure was drawn with MOLSCRIPT^29. b, A
stereo diagram of a C  trace
of the structure, shown in the same orientation as in (a), with
every 20^th residue labeled. c, An orthogonal view drawn as a
CPK representation. Basic residues are in blue, acidic residues
in red, polar residues in pink and hydrophobic residues in
green. The locations of key regions are highlighted. This figure
was drawn with GRASP^30. d, Stereo 2F[o] - F[c] electron density
map (blue), calculated using the final model, at 1.8 Å
resolution. The map is contoured at 1  ,
with the final model overlaid upon it. The region shown
corresponds to part of the hydrophobic core of the protein.
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Figure 3.
Figure 3. Electrostatic surface representations^30 of APP family
members. Blue indicates electropositive potential (> 10 kT)
and red indicates electronegative potential (< -10 kT).
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The above figures are
reprinted
by permission from Macmillan Publishers Ltd:
Nat Struct Biol
(1999,
6,
327-331)
copyright 1999.
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