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| | ==Crystal Structure of Human Galectin-3 CRD in Complex with TD139== | | ==Crystal Structure of Human Galectin-3 CRD in Complex with TD139== |
| - | <StructureSection load='5h9p' size='340' side='right' caption='[[5h9p]], [[Resolution|resolution]] 2.04Å' scene=''> | + | <StructureSection load='5h9p' size='340' side='right'caption='[[5h9p]], [[Resolution|resolution]] 2.04Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5h9p]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5H9P OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5H9P FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5h9p]] 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=5H9P OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5H9P FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><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='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.04Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4xbn|4xbn]], [[5h9q|5h9q]], [[5h9r|5h9r]], [[5h9s|5h9s]]</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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='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=5h9p FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5h9p OCA], [http://pdbe.org/5h9p PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5h9p RCSB], [http://www.ebi.ac.uk/pdbsum/5h9p PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5h9p ProSAT]</span></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=5h9p FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5h9p OCA], [https://pdbe.org/5h9p PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5h9p RCSB], [https://www.ebi.ac.uk/pdbsum/5h9p PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5h9p ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == 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> | + | [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;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </div> | | </div> |
| | <div class="pdbe-citations 5h9p" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 5h9p" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Galectin 3D structures|Galectin 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Hsieh, T J]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Lin, C H]] | + | [[Category: Large Structures]] |
| - | [[Category: Lin, H Y]] | + | [[Category: Hsieh TJ]] |
| - | [[Category: Galectin]] | + | [[Category: Lin CH]] |
| - | [[Category: Pi-arginine interaction]] | + | [[Category: Lin HY]] |
| - | [[Category: Sugar binding protein]]
| + | |
| 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 PubMed
Human galectins are promising targets for cancer immunotherapeutic and fibrotic disease-related drugs. We report herein the binding interactions of three thio-digalactosides (TDGs) including TDG itself, TD139 (3,3'-deoxy-3,3'-bis-(4-[m-fluorophenyl]-1H-1,2,3-triazol-1-yl)-thio-digalactosid e, recently approved for the treatment of idiopathic pulmonary fibrosis), and TAZTDG (3-deoxy-3-(4-[m-fluorophenyl]-1H-1,2,3-triazol-1-yl)-thio-digalactoside) with human galectins-1, -3 and -7 as assessed by X-ray crystallography, isothermal titration calorimetry and NMR spectroscopy. Five binding subsites (A-E) make up the carbohydrate-recognition domains of these galectins. We identified novel interactions between an arginine within subsite E of the galectins and an arene group in the ligands. In addition to the interactions contributed by the galactosyl sugar residues bound at subsites C and D, the fluorophenyl group of TAZTDG preferentially bound to subsite B in galectin-3, whereas the same group favored binding at subsite E in galectins-1 and -7. The characterised dual binding modes demonstrate how binding potency, reported as decreased Kd values of the TDG inhibitors from muM to nM, is improved and also offer insights to development of selective inhibitors for individual galectins.
Dual thio-digalactoside-binding modes of human galectins as the structural basis for the design of potent and selective inhibitors.,Hsieh TJ, Lin HY, Tu Z, Lin TC, Wu SC, Tseng YY, Liu FT, Hsu ST, Lin CH Sci Rep. 2016 Jul 15;6:29457. doi: 10.1038/srep29457. PMID:27416897[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Fukushi J, Makagiansar IT, Stallcup WB. NG2 proteoglycan promotes endothelial cell motility and angiogenesis via engagement of galectin-3 and alpha3beta1 integrin. Mol Biol Cell. 2004 Aug;15(8):3580-90. Epub 2004 Jun 4. PMID:15181153 doi:http://dx.doi.org/10.1091/mbc.E04-03-0236
- ↑ Henderson NC, Sethi T. The regulation of inflammation by galectin-3. Immunol Rev. 2009 Jul;230(1):160-71. doi: 10.1111/j.1600-065X.2009.00794.x. PMID:19594635 doi:10.1111/j.1600-065X.2009.00794.x
- ↑ Haudek KC, Spronk KJ, Voss PG, Patterson RJ, Wang JL, Arnoys EJ. Dynamics of galectin-3 in the nucleus and cytoplasm. Biochim Biophys Acta. 2010 Feb;1800(2):181-189. Epub 2009 Jul 16. PMID:19616076 doi:S0304-4165(09)00194-9
- ↑ Hsieh TJ, Lin HY, Tu Z, Lin TC, Wu SC, Tseng YY, Liu FT, Hsu ST, Lin CH. Dual thio-digalactoside-binding modes of human galectins as the structural basis for the design of potent and selective inhibitors. Sci Rep. 2016 Jul 15;6:29457. doi: 10.1038/srep29457. PMID:27416897 doi:http://dx.doi.org/10.1038/srep29457
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