1rml: Difference between revisions
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|PDB= 1rml |SIZE=350|CAPTION= <scene name='initialview01'>1rml</scene> | |PDB= 1rml |SIZE=350|CAPTION= <scene name='initialview01'>1rml</scene> | ||
|SITE= | |SITE= | ||
|LIGAND= <scene name='pdbligand=NTS:NAPHTHALENE TRISULFONATE'>NTS</scene> | |LIGAND= <scene name='pdbligand=NTS:NAPHTHALENE+TRISULFONATE'>NTS</scene> | ||
|ACTIVITY= | |ACTIVITY= | ||
|GENE= | |GENE= | ||
|DOMAIN= | |||
|RELATEDENTRY= | |||
|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1rml FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1rml OCA], [http://www.ebi.ac.uk/pdbsum/1rml PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1rml RCSB]</span> | |||
}} | }} | ||
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==Overview== | ==Overview== | ||
Recent data show that anti-angiogenesis may provide a promising route to treat cancer. Fibroblast growth factors (FGFs) are powerful angiogenic polypeptides, whose mitogenic activity requires the presence of heparin-like compounds. It has been shown that angiogenesis promoted by FGFs on inhibition by monoclonal antibodies and antisense targeting can also inhibit tumour growth. Derivatives of suramin, a polysulfonated binaphthyl urea and binaphthylsulfonated derivatives of distamycin, suradistas, constitute an important group of potential anti-cancer agents. These compounds compete with heparin in forming tight complexes with FGFs. This inhibits the recognition of these growth factors by their tyrosine kinase membrane receptors thereby suppressing their angiogenic activity. Here we show that 1,3,6-naphthalenetrisulfonate, a common chemical function of the suramins and suradistas with the highest anti-angiogenic activity inhibits the mitogenic activity of acidic fibroblast growth factor, and that this inhibition is relieved by increasing concentrations of heparin in the assay. We have also solved the three-dimensional structure in solution of the protein complexed to this compound. The structural data provide clues that may help in understanding the inhibitory effect of suramins and suradistas, and could contribute to the development of new anti-tumoral drugs. | Recent data show that anti-angiogenesis may provide a promising route to treat cancer. Fibroblast growth factors (FGFs) are powerful angiogenic polypeptides, whose mitogenic activity requires the presence of heparin-like compounds. It has been shown that angiogenesis promoted by FGFs on inhibition by monoclonal antibodies and antisense targeting can also inhibit tumour growth. Derivatives of suramin, a polysulfonated binaphthyl urea and binaphthylsulfonated derivatives of distamycin, suradistas, constitute an important group of potential anti-cancer agents. These compounds compete with heparin in forming tight complexes with FGFs. This inhibits the recognition of these growth factors by their tyrosine kinase membrane receptors thereby suppressing their angiogenic activity. Here we show that 1,3,6-naphthalenetrisulfonate, a common chemical function of the suramins and suradistas with the highest anti-angiogenic activity inhibits the mitogenic activity of acidic fibroblast growth factor, and that this inhibition is relieved by increasing concentrations of heparin in the assay. We have also solved the three-dimensional structure in solution of the protein complexed to this compound. The structural data provide clues that may help in understanding the inhibitory effect of suramins and suradistas, and could contribute to the development of new anti-tumoral drugs. | ||
==About this Structure== | ==About this Structure== | ||
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[[Category: Rico, M.]] | [[Category: Rico, M.]] | ||
[[Category: Santoro, J.]] | [[Category: Santoro, J.]] | ||
[[Category: antitumoral]] | [[Category: antitumoral]] | ||
[[Category: fibroblast growth factor]] | [[Category: fibroblast growth factor]] | ||
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[[Category: naphthalene]] | [[Category: naphthalene]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 23:30:12 2008'' | ||
Revision as of 23:30, 30 March 2008
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| Ligands: | |||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
NMR STUDY OF ACID FIBROBLAST GROWTH FACTOR BOUND TO 1,3,6-NAPHTHALENE TRISULPHONATE, 26 STRUCTURES
OverviewOverview
Recent data show that anti-angiogenesis may provide a promising route to treat cancer. Fibroblast growth factors (FGFs) are powerful angiogenic polypeptides, whose mitogenic activity requires the presence of heparin-like compounds. It has been shown that angiogenesis promoted by FGFs on inhibition by monoclonal antibodies and antisense targeting can also inhibit tumour growth. Derivatives of suramin, a polysulfonated binaphthyl urea and binaphthylsulfonated derivatives of distamycin, suradistas, constitute an important group of potential anti-cancer agents. These compounds compete with heparin in forming tight complexes with FGFs. This inhibits the recognition of these growth factors by their tyrosine kinase membrane receptors thereby suppressing their angiogenic activity. Here we show that 1,3,6-naphthalenetrisulfonate, a common chemical function of the suramins and suradistas with the highest anti-angiogenic activity inhibits the mitogenic activity of acidic fibroblast growth factor, and that this inhibition is relieved by increasing concentrations of heparin in the assay. We have also solved the three-dimensional structure in solution of the protein complexed to this compound. The structural data provide clues that may help in understanding the inhibitory effect of suramins and suradistas, and could contribute to the development of new anti-tumoral drugs.
About this StructureAbout this Structure
1RML is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
ReferenceReference
Solution structure of acidic fibroblast growth factor bound to 1,3, 6-naphthalenetrisulfonate: a minimal model for the anti-tumoral action of suramins and suradistas., Lozano RM, Jimenez M, Santoro J, Rico M, Gimenez-Gallego G, J Mol Biol. 1998 Sep 4;281(5):899-915. PMID:9719643
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