9fdc
From Proteopedia
(Difference between revisions)
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| - | '''Unreleased structure''' | ||
| - | + | ==Co-crystal structure of Galectin-3 with an inhibitor== | |
| + | <StructureSection load='9fdc' size='340' side='right'caption='[[9fdc]], [[Resolution|resolution]] 1.78Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[9fdc]] 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=9FDC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9FDC 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]] 1.78Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=2PE:NONAETHYLENE+GLYCOL'>2PE</scene>, <scene name='pdbligand=A1IB4:(2~{R},3~{R},4~{S},5~{R},6~{R})-~{N}-[3,5-bis(chloranyl)phenyl]-6-(hydroxymethyl)-~{N}-methyl-3,5-bis(oxidanyl)-4-[4-[3,4,5-tris(fluoranyl)phenyl]-1,2,3-triazol-1-yl]oxane-2-carboxamide'>A1IB4</scene>, <scene name='pdbligand=SCN:THIOCYANATE+ION'>SCN</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=9fdc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9fdc OCA], [https://pdbe.org/9fdc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9fdc RCSB], [https://www.ebi.ac.uk/pdbsum/9fdc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9fdc 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 == | ||
| + | Galectin-3 (Gal-3), a beta-galactoside-binding lectin, is implicated in diverse cellular functions ranging from immune response modulation to tissue homeostasis. Notably, increased Gal-3 expression has been linked to the progression of numerous diseases, including cancer, fibrosis, and cardiovascular disorders, underscoring its potential as a therapeutic target. Small molecule inhibitors have been discovered and are valuable tools to study such diseases. We report here the discovery of novel, galactose-based, small molecule inhibitors such as compound 12 which are orally bioavailable and show efficacy in a mouse model of acute liver injury and fibrosis (CCl4 model). The use of structure-based drug design (docking of a virtual library of amides based on acid 2) was key in the process towards potent, nanomolar inhibitors. | ||
| - | + | Discovery of Galactopyranose-1-Carboxamides as a New Class of Small, Novel, Potent, Selective, and Orally Active Galectin-3 Inhibitors.,Zumbrunn C, Remen L, Sager CP, Grisostomi C, Stamm C, Krusi D, Glutz S, Schmidt G, Nayler O, Iglarz M, Mac Sweeney A, Chambovey A, Muller M, Mueller C, Huhn E, Cattaneo C, Vercauteren M, Gatfield J, Bolli MH, Meyer S, Bourquin G ChemMedChem. 2025 Mar 12:e202401012. doi: 10.1002/cmdc.202401012. PMID:40071533<ref>PMID:40071533</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| + | <div class="pdbe-citations 9fdc" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Mac Sweeney A]] | ||
Revision as of 21:46, 26 March 2025
Co-crystal structure of Galectin-3 with an inhibitor
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