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== | ==A complex between acidic fibroblast growth factor and 5-amino-2-naphthalenesulfonate== | ||
Inhibition of angiogenesis-promoting factors such as fibroblast growth | <StructureSection load='1hkn' size='340' side='right'caption='[[1hkn]], [[Resolution|resolution]] 2.00Å' scene=''> | ||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[1hkn]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1HKN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1HKN FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=N2M:5-AMINO-NAPHTALENE-2-MONOSULFONATE'>N2M</scene></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1hkn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1hkn OCA], [https://pdbe.org/1hkn PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1hkn RCSB], [https://www.ebi.ac.uk/pdbsum/1hkn PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1hkn ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/FGF1_HUMAN FGF1_HUMAN] Plays an important role in the regulation of cell survival, cell division, angiogenesis, cell differentiation and cell migration. Functions as potent mitogen in vitro.<ref>PMID:8663044</ref> <ref>PMID:16597617</ref> <ref>PMID:20145243</ref> | |||
== Evolutionary Conservation == | |||
[[Image:Consurf_key_small.gif|200px|right]] | |||
Check<jmol> | |||
<jmolCheckbox> | |||
<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/hk/1hkn_consurf.spt"</scriptWhenChecked> | |||
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | |||
<text>to colour the structure by Evolutionary Conservation</text> | |||
</jmolCheckbox> | |||
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1hkn ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Inhibition of angiogenesis-promoting factors such as fibroblast growth factors is considered to be a potential procedure for inhibiting solid tumor growth. Although several peptide-based inhibitors are currently under study, the development of antiangiogenic compounds of small molecular size is a pharmacological goal of considerable interest. We have already shown that certain naphthalene sulfonates constitute minimal functional substitutes of the antiangiogenic compounds of the suramin and suradista family. Using those data as a lead, we have carried out a rational search for new angiogenesis inhibitors that could provide new pharmacological insights for the development of antiangiogenic treatments. The results of the study strongly underline the relevance of the stereochemistry for an efficient inhibition of acidic fibroblast growth factor mitogenic activity by the naphthalene sulfonate family and allow us to formulate rules to aid in searching for new inhibitors and pharmaceutical developments. To provide further leads for such developments and acquire a detailed insight into the basis of the inhibitory activity of the naphthalene sulfonate derivatives, we solved the three-dimensional structure of acidic fibroblast growth factor complexed to 5-amino-2-naphthalenesulfonate, the most pharmacologically promising of the identified inhibitors. The structure shows that binding of this compound would hamper the interaction of acidic fibroblast growth factor with the different components of the cell membrane mitogenesis-triggering complex. | |||
Leads for development of new naphthalenesulfonate derivatives with enhanced antiangiogenic activity: crystal structure of acidic fibroblast growth factor in complex with 5-amino-2-naphthalene sulfonate.,Fernandez-Tornero C, Lozano RM, Redondo-Horcajo M, Gomez AM, Lopez JC, Quesada E, Uriel C, Valverde S, Cuevas P, Romero A, Gimenez-Gallego G J Biol Chem. 2003 Jun 13;278(24):21774-81. Epub 2003 Apr 3. PMID:12676958<ref>PMID:12676958</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 1hkn" style="background-color:#fffaf0;"></div> | |||
== | ==See Also== | ||
*[[Fibroblast growth factor 3D structures|Fibroblast growth factor 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: Fernandez-Tornero | [[Category: Fernandez-Tornero C]] | ||
[[Category: Gimenez-Gallego | [[Category: Gimenez-Gallego G]] | ||
[[Category: Lozano | [[Category: Lozano RM]] | ||
[[Category: Romero | [[Category: Romero A]] | ||
Latest revision as of 15:28, 13 December 2023
A complex between acidic fibroblast growth factor and 5-amino-2-naphthalenesulfonateA complex between acidic fibroblast growth factor and 5-amino-2-naphthalenesulfonate
Structural highlights
FunctionFGF1_HUMAN Plays an important role in the regulation of cell survival, cell division, angiogenesis, cell differentiation and cell migration. Functions as potent mitogen in vitro.[1] [2] [3] 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 PubMedInhibition of angiogenesis-promoting factors such as fibroblast growth factors is considered to be a potential procedure for inhibiting solid tumor growth. Although several peptide-based inhibitors are currently under study, the development of antiangiogenic compounds of small molecular size is a pharmacological goal of considerable interest. We have already shown that certain naphthalene sulfonates constitute minimal functional substitutes of the antiangiogenic compounds of the suramin and suradista family. Using those data as a lead, we have carried out a rational search for new angiogenesis inhibitors that could provide new pharmacological insights for the development of antiangiogenic treatments. The results of the study strongly underline the relevance of the stereochemistry for an efficient inhibition of acidic fibroblast growth factor mitogenic activity by the naphthalene sulfonate family and allow us to formulate rules to aid in searching for new inhibitors and pharmaceutical developments. To provide further leads for such developments and acquire a detailed insight into the basis of the inhibitory activity of the naphthalene sulfonate derivatives, we solved the three-dimensional structure of acidic fibroblast growth factor complexed to 5-amino-2-naphthalenesulfonate, the most pharmacologically promising of the identified inhibitors. The structure shows that binding of this compound would hamper the interaction of acidic fibroblast growth factor with the different components of the cell membrane mitogenesis-triggering complex. Leads for development of new naphthalenesulfonate derivatives with enhanced antiangiogenic activity: crystal structure of acidic fibroblast growth factor in complex with 5-amino-2-naphthalene sulfonate.,Fernandez-Tornero C, Lozano RM, Redondo-Horcajo M, Gomez AM, Lopez JC, Quesada E, Uriel C, Valverde S, Cuevas P, Romero A, Gimenez-Gallego G J Biol Chem. 2003 Jun 13;278(24):21774-81. Epub 2003 Apr 3. PMID:12676958[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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