5oax
From Proteopedia
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| - | '''Unreleased structure''' | ||
| - | + | ==Galectin-3c in complex with thiogalactoside derivate== | |
| + | <StructureSection load='5oax' size='340' side='right' caption='[[5oax]], [[Resolution|resolution]] 1.20Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[5oax]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5OAX OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5OAX FirstGlance]. <br> | ||
| + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=9Q5:5,6-bis(fluoranyl)-3-[[(2~{S},3~{R},4~{S},5~{S},6~{R})-2-[(2~{S},3~{R},4~{S},5~{R},6~{R})-4-[4-(3-fluorophenyl)-1,2,3-triazol-1-yl]-6-(hydroxymethyl)-3,5-bis(oxidanyl)oxan-2-yl]sulfanyl-6-(hydroxymethyl)-3,5-bis(oxidanyl)oxan-4-yl]oxymethyl]chromen-2-one'>9Q5</scene></td></tr> | ||
| + | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4bli|4bli]]</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=5oax FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5oax OCA], [http://pdbe.org/5oax PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5oax RCSB], [http://www.ebi.ac.uk/pdbsum/5oax PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5oax 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 == | ||
| + | Symmetrical and asymmetrical fluorinated phenyltriazolyl-thiodigalactoside derivatives have been synthesized and evaluated as inhibitors of galectin-1 and galectin-3. Systematic tuning of the phenyltriazolyl-thiodigalactosides' fluoro-interactions with galectin-3 led to the discovery of inhibitors with exceptional affinities (Kd down to 1-2 nM) in symmetrically substituted thiodigalactosides as well as unsurpassed combination of high affinity (Kd 7.5 nM) and selectivity (46-fold) over galectin-1 for asymmetrical thiodigalactosides by carrying one trifluorphenyltriazole and one coumaryl moiety. Studies of the inhibitor-galectin complexes with isothermal titration calorimetry and X-ray crystallography revealed the importance of fluoro-amide interaction for affinity and for selectivity. Finally, the high affinity of the discovered inhibitors required two competitive titration assay tools to be developed: a new high affinity fluorescent probe for competitive fluorescent polarization and a competitive ligand optimal for analyzing high affinity galectin-3 inhibitors with competitive isothermal titration calorimetry. | ||
| - | + | Systematic Tuning of Fluoro-galectin-3 Interactions Provides Thiodigalactoside Derivatives with Single-Digit nM Affinity and High Selectivity.,Peterson K, Kumar R, Stenstrom O, Verma P, Verma PR, Hakansson M, Kahl-Knutsson B, Zetterberg F, Leffler H, Akke M, Logan DT, Nilsson UJ J Med Chem. 2018 Feb 8;61(3):1164-1175. doi: 10.1021/acs.jmedchem.7b01626. Epub, 2018 Jan 11. PMID:29284090<ref>PMID:29284090</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| + | <div class="pdbe-citations 5oax" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Hakansson, M]] | ||
| + | [[Category: Logan, D T]] | ||
| + | [[Category: Nilsson, U J]] | ||
[[Category: Peterson, K]] | [[Category: Peterson, K]] | ||
| - | [[Category: | + | [[Category: Sugar binding protein]] |
Revision as of 07:58, 2 May 2018
Galectin-3c in complex with thiogalactoside derivate
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