6g0v: Difference between revisions
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==Human Galectin-3 in complex with a TF tumor-associated antigen mimetic== | |||
<StructureSection load='6g0v' size='340' side='right' caption='[[6g0v]], [[Resolution|resolution]] 1.09Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[6g0v]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6G0V OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6G0V FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=EGZ:(3~{R},5~{R},6~{S},7~{S},8~{R},13~{S})-5-(hydroxymethyl)-7-[(2~{S},3~{R},4~{S},5~{R},6~{R})-6-(hydroxymethyl)-3,4,5-tris(oxidanyl)oxan-2-yl]oxy-6-oxidanyl-11-oxidanylidene-2,4-dioxa-9-thia-12-azatricyclo[8.4.0.0^{3,8}]tetradec-1(10)-ene-13-carboxylic+acid'>EGZ</scene></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6g0v FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6g0v OCA], [http://pdbe.org/6g0v PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6g0v RCSB], [http://www.ebi.ac.uk/pdbsum/6g0v PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6g0v ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[[http://www.uniprot.org/uniprot/LEG3_HUMAN LEG3_HUMAN]] Galactose-specific lectin which binds IgE. May mediate with the alpha-3, beta-1 integrin the stimulation by CSPG4 of endothelial cells migration. Together with DMBT1, required for terminal differentiation of columnar epithelial cells during early embryogenesis (By similarity). In the nucleus: acts as a pre-mRNA splicing factor. Involved in acute inflammatory responses including neutrophil activation and adhesion, chemoattraction of monocytes macrophages, opsonization of apoptotic neutrophils, and activation of mast cells.<ref>PMID:15181153</ref> <ref>PMID:19594635</ref> <ref>PMID:19616076</ref> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Overexpression of the Thomsen-Friedenreich (TF) antigen in cell membrane proteins occurs in 90% of adenocarcinomas. Additionally, the binding of the TF-antigen to human galectin-3 (Gal-3), also frequently overexpressed in malignancy, promotes cancer progression and metastasis. In this context, structures that interfere with this specific interaction display the potential to prevent cancer metastasis. Herein, a multidisciplinary approach, combining the optimized synthesis of a TF-antigen mimetic with NMR, X-ray crystallography methods and isothermal titration calorimetry assays has been employed to unravel the molecular structural details that govern the Gal-3/TF-mimetic interaction. The TF-mimetic presents a binding affinity for Gal-3 similar to the TF-natural antigen and retains the binding epitope and the bioactive conformation observed for the native antigen. Furthermore, from a thermodynamic perspective a decrease in the enthalpic contribution was observed for the Gal-3/TF-mimetic complex, however this behaviour is compensated by a favourable entropy gain. From a structural perspective, these results establish our TF-mimetic as a scaffold to design multivalent solutions to potentially interfere with Gal-3 aberrant interactions and likely be used to hamper Gal-3-mediated cancer cells adhesion and metastasis. | |||
Molecular recognition of a Thomsen-Friedenreich antigen mimetic targeting human galectin-3.,Santarsia S, Grosso AS, Trovao F, Jimenez-Barbero J, Carvalho AL, Nativi C, Marcelo F ChemMedChem. 2018 Aug 9. doi: 10.1002/cmdc.201800525. PMID:30094951<ref>PMID:30094951</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 6g0v" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Carvalho, A L]] | |||
[[Category: Santarsia, S]] | [[Category: Santarsia, S]] | ||
[[Category: Trovao, F | [[Category: Trovao, F G]] | ||
[[Category: | [[Category: Cancer]] | ||
[[Category: Cell adhesion]] | |||
[[Category: Galectin-3]] | |||
[[Category: Tf-mimetic]] | |||
[[Category: Thomsen-friedenreich]] | |||
[[Category: Tumour antigen]] | |||
Revision as of 09:16, 22 August 2018
Human Galectin-3 in complex with a TF tumor-associated antigen mimeticHuman Galectin-3 in complex with a TF tumor-associated antigen mimetic
Structural highlights
Function[LEG3_HUMAN] Galactose-specific lectin which binds IgE. May mediate with the alpha-3, beta-1 integrin the stimulation by CSPG4 of endothelial cells migration. Together with DMBT1, required for terminal differentiation of columnar epithelial cells during early embryogenesis (By similarity). In the nucleus: acts as a pre-mRNA splicing factor. Involved in acute inflammatory responses including neutrophil activation and adhesion, chemoattraction of monocytes macrophages, opsonization of apoptotic neutrophils, and activation of mast cells.[1] [2] [3] Publication Abstract from PubMedOverexpression of the Thomsen-Friedenreich (TF) antigen in cell membrane proteins occurs in 90% of adenocarcinomas. Additionally, the binding of the TF-antigen to human galectin-3 (Gal-3), also frequently overexpressed in malignancy, promotes cancer progression and metastasis. In this context, structures that interfere with this specific interaction display the potential to prevent cancer metastasis. Herein, a multidisciplinary approach, combining the optimized synthesis of a TF-antigen mimetic with NMR, X-ray crystallography methods and isothermal titration calorimetry assays has been employed to unravel the molecular structural details that govern the Gal-3/TF-mimetic interaction. The TF-mimetic presents a binding affinity for Gal-3 similar to the TF-natural antigen and retains the binding epitope and the bioactive conformation observed for the native antigen. Furthermore, from a thermodynamic perspective a decrease in the enthalpic contribution was observed for the Gal-3/TF-mimetic complex, however this behaviour is compensated by a favourable entropy gain. From a structural perspective, these results establish our TF-mimetic as a scaffold to design multivalent solutions to potentially interfere with Gal-3 aberrant interactions and likely be used to hamper Gal-3-mediated cancer cells adhesion and metastasis. Molecular recognition of a Thomsen-Friedenreich antigen mimetic targeting human galectin-3.,Santarsia S, Grosso AS, Trovao F, Jimenez-Barbero J, Carvalho AL, Nativi C, Marcelo F ChemMedChem. 2018 Aug 9. doi: 10.1002/cmdc.201800525. PMID:30094951[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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