5e88
From Proteopedia
(Difference between revisions)
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| - | '''Unreleased structure''' | ||
| - | + | ==Crystal structure of Human galectin-3 CRD in complex with thienyl-1,2,3-triazolyl thiodigalactoside inhibitor== | |
| + | <StructureSection load='5e88' size='340' side='right' caption='[[5e88]], [[Resolution|resolution]] 1.60Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[5e88]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5E88 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5E88 FirstGlance]. <br> | ||
| + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=5KT:3-DEOXY-3-[4-(THIOPHEN-3-YL)-1H-1,2,3-TRIAZOL-1-YL]-BETA-D-GALACTOPYRANOSYL+3-DEOXY-1-THIO-3-[4-(THIOPHEN-3-YL)-1H-1,2,3-TRIAZOL-1-YL]-BETA-D-GALACTOPYRANOSIDE'>5KT</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">[[5e8a|5e8a]], [[5e89|5e89]]</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=5e88 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5e88 OCA], [http://pdbe.org/5e88 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5e88 RCSB], [http://www.ebi.ac.uk/pdbsum/5e88 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5e88 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 == | ||
| + | Discovery 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<ref>PMID:27356186</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | + | </div> | |
| + | <div class="pdbe-citations 5e88" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
[[Category: Blanchard, H]] | [[Category: Blanchard, H]] | ||
| - | [[Category: Collins, P | + | [[Category: Collins, P M]] |
| + | [[Category: Beta sandwich]] | ||
| + | [[Category: Carbohydrate binding protein]] | ||
| + | [[Category: Carbohydrate-recognition]] | ||
| + | [[Category: Sugar binding protein]] | ||
| + | [[Category: Sugar binding protein-inhibitor complex]] | ||
Revision as of 06:50, 10 September 2016
Crystal structure of Human galectin-3 CRD in complex with thienyl-1,2,3-triazolyl thiodigalactoside inhibitor
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