4jck: Difference between revisions
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==Galectin-3 carbohydrate recognition domain in complex with thioditaloside== | |||
===Galectin-3 carbohydrate recognition domain in | <StructureSection load='4jck' size='340' side='right' caption='[[4jck]], [[Resolution|resolution]] 1.15Å' scene=''> | ||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[4jck]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4JCK OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4JCK FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=1LL:THIODITALOSIDE'>1LL</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene></td></tr> | |||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4jc1|4jc1]]</td></tr> | |||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">LGALS3, MAC2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</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=4jck FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4jck OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4jck RCSB], [http://www.ebi.ac.uk/pdbsum/4jck PDBsum]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Galectin-3 is extensively involved in metabolic and disease processes, such as cancer metastasis, thus giving impetus for the design of specific inhibitors targeting this beta-galactose-binding protein. Thiodigalactoside (TDG) presents a scaffold for construction of galectin inhibitors, and its inhibition of galectin-1 has already demonstrated beneficial effects as an adjuvant with vaccine immunotherapy, thereby improving the survival outcome of tumour-challenged mice. A novel approach-replacing galactose with its C2 epimer, talose-offers an alternative framework, as extensions at C2 permit exploitation of a galectin-3-specific binding groove, thereby facilitating the design of selective inhibitors. We report the synthesis of thioditaloside (TDT) and crystal structures of the galectin-3 carbohydrate recognition domain in complexes with TDT and TDG. The different abilities of galactose and talose to anchor to the protein correlate with molecular dynamics studies, likely explaining the relative disaccharide binding affinities. The feasibility of a TDT scaffold to enable access to a particular galectin-3 binding groove and the need for modifications to optimise such a scaffold for use in the design of potent and selective inhibitors are assessed. | |||
Investigation into the feasibility of thioditaloside as a novel scaffold for galectin-3-specific inhibitors.,Bum-Erdene K, Gagarinov IA, Collins PM, Winger M, Pearson AG, Wilson JC, Leffler H, Nilsson UJ, Grice ID, Blanchard H Chembiochem. 2013 Jul 22;14(11):1331-42. doi: 10.1002/cbic.201300245. PMID:23864426<ref>PMID:23864426</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
== | ==See Also== | ||
*[[Galectin|Galectin]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Blanchard, H | [[Category: Blanchard, H]] | ||
[[Category: Bum-Erdene, K | [[Category: Bum-Erdene, K]] | ||
[[Category: Beta sandwich]] | [[Category: Beta sandwich]] | ||
[[Category: Carbohydrate binding protein]] | [[Category: Carbohydrate binding protein]] | ||
[[Category: Sugar binding protein-inhibitor complex]] | [[Category: Sugar binding protein-inhibitor complex]] | ||
Revision as of 16:06, 21 December 2014
Galectin-3 carbohydrate recognition domain in complex with thioditalosideGalectin-3 carbohydrate recognition domain in complex with thioditaloside
Structural highlights
Publication Abstract from PubMedGalectin-3 is extensively involved in metabolic and disease processes, such as cancer metastasis, thus giving impetus for the design of specific inhibitors targeting this beta-galactose-binding protein. Thiodigalactoside (TDG) presents a scaffold for construction of galectin inhibitors, and its inhibition of galectin-1 has already demonstrated beneficial effects as an adjuvant with vaccine immunotherapy, thereby improving the survival outcome of tumour-challenged mice. A novel approach-replacing galactose with its C2 epimer, talose-offers an alternative framework, as extensions at C2 permit exploitation of a galectin-3-specific binding groove, thereby facilitating the design of selective inhibitors. We report the synthesis of thioditaloside (TDT) and crystal structures of the galectin-3 carbohydrate recognition domain in complexes with TDT and TDG. The different abilities of galactose and talose to anchor to the protein correlate with molecular dynamics studies, likely explaining the relative disaccharide binding affinities. The feasibility of a TDT scaffold to enable access to a particular galectin-3 binding groove and the need for modifications to optimise such a scaffold for use in the design of potent and selective inhibitors are assessed. Investigation into the feasibility of thioditaloside as a novel scaffold for galectin-3-specific inhibitors.,Bum-Erdene K, Gagarinov IA, Collins PM, Winger M, Pearson AG, Wilson JC, Leffler H, Nilsson UJ, Grice ID, Blanchard H Chembiochem. 2013 Jul 22;14(11):1331-42. doi: 10.1002/cbic.201300245. PMID:23864426[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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