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PDBsum entry 1afc
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Growth factor
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PDB id
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1afc
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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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Structural studies of the binding of the anti-Ulcer drug sucrose octasulfate to acidic fibroblast growth factor.
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Authors
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X.Zhu,
B.T.Hsu,
D.C.Rees.
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Ref.
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Structure, 1993,
1,
27-34.
[DOI no: ]
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PubMed id
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Abstract
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BACKGROUND: The anti-ulcer drug sucrose octasulfate (SOS) binds to fibroblast
growth factors (FGFs), proteins which stimulate the growth and differentiation
of several cell types, including stomach epithelial cells. It is believed that
SOS stabilizes FGFs against acid denaturation in the stomach, thus enhancing
their ability to stimulate healing of ulcerated tissue. SOS binds to the same
site on FGF as heparin and other proteoglycans; in vivo, FGF must bind to
cell-surface proteoglycans or to heparin before it can interact with FGF
receptors and stimulate growth. The details of this process are not understood.
RESULTS: We report the crystal structure of a 1:1 complex between acidic FGF
(aFGF) and SOS at 2.7 A resolution. SOS binds to a positively charged region of
aFGF, largely composed of residues 112-127, and makes contacts primarily with
Lys112, Arg116, Lys118, and Arg122. This region is also important in binding
heparin. The overall conformation of aFGF is not changed by binding SOS,
although the positions of some side chains in the binding site shift by as much
as 6 A. CONCLUSION: The SOS-FGF crystal structure is consistent with the model
that SOS stabilizes FGF by neutralizing several positively charged residues that
would destabilize the native structure by electrostatic repulsion. On the basis
of this structure, we provide a model for the complex of heparin with an FGF
dimer. Such interactions may facilitate FGF receptor dimerization, which may be
important in receptor signaling.
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Secondary reference #1
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Title
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Three-Dimensional structures of acidic and basic fibroblast growth factors.
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Authors
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X.Zhu,
H.Komiya,
A.Chirino,
S.Faham,
G.M.Fox,
T.Arakawa,
B.T.Hsu,
D.C.Rees.
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Ref.
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Science, 1991,
251,
90-93.
[DOI no: ]
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PubMed id
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