5ody: Difference between revisions
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==Galectin-3C in complex with dithiogalactoside derivative== | |||
<StructureSection load='5ody' size='340' side='right'caption='[[5ody]], [[Resolution|resolution]] 1.15Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[5ody]] is a 1 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=5ODY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5ODY 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]] 1.149Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=9SK:5,6-bis(fluoranyl)-3-[[(2~{R},3~{S},4~{S},5~{R},6~{S})-2-(hydroxymethyl)-6-[(2~{S},3~{R},4~{S},5~{R},6~{R})-6-(hydroxymethyl)-3,5-bis(oxidanyl)-4-[4-[3,4,5-tris(fluoranyl)phenyl]-1,2,3-triazol-1-yl]oxan-2-yl]sulfanyl-3,5-bis(oxidanyl)oxan-4-yl]oxymethyl]chromen-2-one'>9SK</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=5ody FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ody OCA], [https://pdbe.org/5ody PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5ody RCSB], [https://www.ebi.ac.uk/pdbsum/5ody PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5ody ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://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> | ||
[[Category: Kumar | <div class="pdbe-citations 5ody" style="background-color:#fffaf0;"></div> | ||
[[Category: Logan | |||
[[Category: | ==See Also== | ||
[[Category: | *[[Galectin 3D structures|Galectin 3D structures]] | ||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: Kumar R]] | |||
[[Category: Logan DT]] | |||
[[Category: Nilsson UJ]] | |||
[[Category: Peterson K]] | |||