5e89: Difference between revisions
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==Crystal structure of Human galectin-3 CRD in complex with 3-fluophenyl-1,2,3-triazolyl thiodigalactoside inhibitor== | ==Crystal structure of Human galectin-3 CRD in complex with 3-fluophenyl-1,2,3-triazolyl thiodigalactoside inhibitor== | ||
<StructureSection load='5e89' size='340' side='right' caption='[[5e89]], [[Resolution|resolution]] 1.50Å' scene=''> | <StructureSection load='5e89' size='340' side='right'caption='[[5e89]], [[Resolution|resolution]] 1.50Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[5e89]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5E89 OCA]. For a <b>guided tour on the structure components</b> use [http:// | <table><tr><td colspan='2'>[[5e89]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5E89 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5E89 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=TD2:3-DEOXY-3-[4-(3-FLUOROPHENYL)-1H-1,2,3-TRIAZOL-1-YL]-BETA-D-GALACTOPYRANOSYL+3-DEOXY-3-[4-(3-FLUOROPHENYL)-1H-1,2,3-TRIAZOL-1-YL]-1-THIO-BETA-D-GALACTOPYRANOSIDE'>TD2</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=TD2:3-DEOXY-3-[4-(3-FLUOROPHENYL)-1H-1,2,3-TRIAZOL-1-YL]-BETA-D-GALACTOPYRANOSYL+3-DEOXY-3-[4-(3-FLUOROPHENYL)-1H-1,2,3-TRIAZOL-1-YL]-1-THIO-BETA-D-GALACTOPYRANOSIDE'>TD2</scene></td></tr> | ||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5e88|5e88]], [[5e8a|5e8a]]</td></tr> | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5e88|5e88]], [[5e8a|5e8a]]</td></tr> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http:// | <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 HUMAN])</td></tr> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=5e89 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5e89 OCA], [http://pdbe.org/5e89 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5e89 RCSB], [http://www.ebi.ac.uk/pdbsum/5e89 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5e89 ProSAT]</span></td></tr> | |||
</table> | </table> | ||
== Function == | == Function == | ||
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</div> | </div> | ||
<div class="pdbe-citations 5e89" style="background-color:#fffaf0;"></div> | <div class="pdbe-citations 5e89" style="background-color:#fffaf0;"></div> | ||
==See Also== | |||
*[[Galectin 3D structures|Galectin 3D structures]] | |||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Human]] | |||
[[Category: Large Structures]] | |||
[[Category: Blanchard, H]] | [[Category: Blanchard, H]] | ||
[[Category: Collins, P M]] | [[Category: Collins, P M]] | ||
Revision as of 09:47, 22 April 2020
Crystal structure of Human galectin-3 CRD in complex with 3-fluophenyl-1,2,3-triazolyl thiodigalactoside inhibitorCrystal structure of Human galectin-3 CRD in complex with 3-fluophenyl-1,2,3-triazolyl thiodigalactoside inhibitor
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 PubMedDiscovery of glycan-competitive galectin-3-binding compounds that attenuate lung fibrosis in a murine model and that block intracellular galectin-3 accumulation at damaged vesicles, hence revealing galectin-3-glycan interactions involved in fibrosis progression and in intracellular galectin-3 activities, is reported. 3,3'-Bis-(4-aryltriazol-1-yl)thiodigalactosides were synthesized and evaluated as antagonists of galectin-1, -2, -3, and -4 N-terminal, -4 C-terminal, -7 and -8 N-terminal, -9 N-terminal, and -9 C-terminal domains. Compounds displaying low-nanomolar affinities for galectins-1 and -3 were identified in a competitive fluorescence anisotropy assay. X-ray structural analysis of selected compounds in complex with galectin-3, together with galectin-3 mutant binding experiments, revealed that both the aryltriazolyl moieties and fluoro substituents on the compounds are involved in key interactions responsible for exceptional affinities towards galectin-3. The most potent galectin-3 antagonist was demonstrated to act in an assay monitoring galectin-3 accumulation upon amitriptyline-induced vesicle damage, visualizing a biochemically/medically relevant intracellular lectin-carbohydrate binding event and that it can be blocked by a small molecule. The same antagonist administered intratracheally attenuated bleomycin-induced pulmonary fibrosis in a mouse model with a dose/response profile comparing favorably with that of oral administration of the marketed antifibrotic compound pirfenidone. Galectin-3-Binding Glycomimetics that Strongly Reduce Bleomycin-Induced Lung Fibrosis and Modulate Intracellular Glycan Recognition.,Delaine T, Collins P, MacKinnon A, Sharma G, Stegmayr J, Rajput VK, Mandal S, Cumpstey I, Larumbe A, Salameh BA, Kahl-Knutsson B, van Hattum H, van Scherpenzeel M, Pieters RJ, Sethi T, Schambye H, Oredsson S, Leffler H, Blanchard H, Nilsson UJ Chembiochem. 2016 Jun 29. doi: 10.1002/cbic.201600285. PMID:27356186[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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