1afc

STRUCTURAL STUDIES OF THE BINDING OF THE ANTI-ULCER DRUG SUCROSE OCTASULFATE TO ACIDIC FIBROBLAST GROWTH FACTOR

spinqualitylabelsall models 1afc, resolution 2.70Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 1afc is a 8 chain structure with sequence from Bovin. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: SCR Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [FGF1_BOVIN] Plays an important role in the regulation of cell survival, cell division, angiogenesis, cell differentiation and cell migration. Functions as potent mitogen in vitro. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed 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. Structural studies of the binding of the anti-ulcer drug sucrose octasulfate to acidic fibroblast growth factor.,Zhu X, Hsu BT, Rees DC Structure. 1993 Sep 15;1(1):27-34. PMID:7520817 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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