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PDBsum entry 1a3p
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Growth factor
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PDB id
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1a3p
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Contents |
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* Residue conservation analysis
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PDB id:
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Growth factor
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Title:
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Role of the 6-20 disulfide bridge in the structure and activity of epidermal growth factor, nmr, 20 structures
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Structure:
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Epidermal growth factor. Chain: a. Fragment: residues 4 - 48. Synonym: [abu6, 20] megf4-48. Engineered: yes. Mutation: yes
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Source:
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Mus musculus. House mouse. Organism_taxid: 10090
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NMR struc:
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20 models
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Authors:
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K.Barnham,A.Torres,D.Alewood,P.Alewood,T.Domagala,E.Nice,R.Norton
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Key ref:
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K.J.Barnham
et al.
(1998).
Role of the 6-20 disulfide bridge in the structure and activity of epidermal growth factor.
Protein Sci,
7,
1738-1749.
PubMed id:
DOI:
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Date:
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22-Jan-98
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Release date:
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29-Jul-98
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PROCHECK
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Headers
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References
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P01132
(EGF_MOUSE) -
Pro-epidermal growth factor from Mus musculus
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Seq:
Struc:
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1217 a.a.
45 a.a.*
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Key: |
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Secondary structure |
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CATH domain |
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*
PDB and UniProt seqs differ
at 2 residue positions (black
crosses)
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DOI no:
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Protein Sci
7:1738-1749
(1998)
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PubMed id:
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Role of the 6-20 disulfide bridge in the structure and activity of epidermal growth factor.
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K.J.Barnham,
A.M.Torres,
D.Alewood,
P.F.Alewood,
T.Domagala,
E.C.Nice,
R.S.Norton.
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ABSTRACT
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Two synthetic analogues of murine epidermal growth factor, [Abu6, 20] mEGF4-48
(where Abu denotes amino-butyric acid) and [G1, M3, K21, H40] mEGF1-48, have
been investigated by NMR spectroscopy. [Abu6, 20] mEGF4-48 was designed to
determine the contribution of the 6-20 disulfide bridge to the structure and
function of mEGF. The overall structure of this analogue was similar to that of
native mEGF, indicating that the loss of the 6-20 disulfide bridge did not
affect the global fold of the molecule. Significant structural differences were
observed near the N-terminus, however, with the direction of the polypeptide
chain between residues four and nine being altered such that these residues were
now located on the opposite face of the main beta-sheet from their position in
native mEGF. Thermal denaturation experiments also showed that the structure of
[Abu6, 20] mEGF4-48 was less stable than that of mEGF. Removal of this disulfide
bridge resulted in a significant loss of both mitogenic activity in Balb/c 3T3
cells and receptor binding on A431 cells compared with native mEGF and mEGF4-48,
implying that the structural changes in [Abu6, 20] mEGF4-48, although limited to
the N-terminus, were sufficient to interfere with receptor binding. The loss of
binding affinity probably arose mainly from steric interactions of the
dislocated N-terminal region with part of the receptor binding surface of EGF.
[G1, M3, K21, H40] mEGF1-48 was also synthesized in order to compare the
synthetic polypeptide with the corresponding product of recombinant expression.
Its mitogenic activity in Balb/c 3T3 cells was similar to that of native mEGF
and analysis of its 1H chemical shifts suggested that its structure was also
very similar to native.
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Selected figure(s)
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Figure 6.
Fig. 6. Stereo view of thebackbone atoms
and disulfide bonds of thefinal 20 structures of [Abu6.
201 mEGF4-48inwater,superimposed over theback-
bone heavy atoms (N, C, C) of the well-defined (Sd
and S, > 0.8) of he molecule, encompassing
residues 6-46.
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Figure 7.
Fig. 7.
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The above figures are
reprinted
by permission from the Protein Society:
Protein Sci
(1998,
7,
1738-1749)
copyright 1998.
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Figures were
selected
by an automated process.
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Literature references that cite this PDB file's key reference
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Google scholar
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PubMed id
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Reference
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M.E.McMellen,
D.Wakeman,
S.W.Longshore,
L.A.McDuffie,
and
B.W.Warner
(2010).
Growth factors: possible roles for clinical management of the short bowel syndrome.
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Semin Pediatr Surg,
19,
35-43.
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J.T.Hoskins,
Z.Zhou,
and
P.A.Harding
(2008).
The significance of disulfide bonding in biological activity of HB-EGF, a mutagenesis approach.
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Biochem Biophys Res Commun,
375,
506-511.
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F.Zanuttin,
C.Guarnaccia,
A.Pintar,
and
S.Pongor
(2004).
Folding of epidermal growth factor-like repeats from human tenascin studied through a sequence frame-shift approach.
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Eur J Biochem,
271,
4229-4240.
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T.P.Garrett,
N.M.McKern,
M.Lou,
T.C.Elleman,
T.E.Adams,
G.O.Lovrecz,
H.J.Zhu,
F.Walker,
M.J.Frenkel,
P.A.Hoyne,
R.N.Jorissen,
E.C.Nice,
A.W.Burgess,
and
C.W.Ward
(2002).
Crystal structure of a truncated epidermal growth factor receptor extracellular domain bound to transforming growth factor alpha.
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Cell,
110,
763-773.
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PDB code:
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The most recent references are shown first.
Citation data come partly from CiteXplore and partly
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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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