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| | <StructureSection load='6eol' size='340' side='right'caption='[[6eol]], [[Resolution|resolution]] 1.50Å' scene=''> | | <StructureSection load='6eol' size='340' side='right'caption='[[6eol]], [[Resolution|resolution]] 1.50Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6eol]] 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=6EOL OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6EOL FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6eol]] 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=6EOL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6EOL FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BKH:(2~{R},3~{R},4~{S},5~{R},6~{R})-2-(3,4-dichlorophenyl)sulfanyl-6-(hydroxymethyl)-4-[4-[3,4,5-tris(fluoranyl)phenyl]-1,2,3-triazol-1-yl]oxane-3,5-diol'>BKH</scene>, <scene name='pdbligand=SCN:THIOCYANATE+ION'>SCN</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]] 1.5Å</td></tr> |
| - | <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='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BKH:(2~{R},3~{R},4~{S},5~{R},6~{R})-2-(3,4-dichlorophenyl)sulfanyl-6-(hydroxymethyl)-4-[4-[3,4,5-tris(fluoranyl)phenyl]-1,2,3-triazol-1-yl]oxane-3,5-diol'>BKH</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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6eol FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6eol OCA], [http://pdbe.org/6eol PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6eol RCSB], [http://www.ebi.ac.uk/pdbsum/6eol PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6eol 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=6eol FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6eol OCA], [https://pdbe.org/6eol PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6eol RCSB], [https://www.ebi.ac.uk/pdbsum/6eol PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6eol 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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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Hakansson, M]] | + | [[Category: Hakansson M]] |
| - | [[Category: Logan, D T]] | + | [[Category: Logan DT]] |
| - | [[Category: Nilsson, U J]] | + | [[Category: Nilsson UJ]] |
| - | [[Category: Zetterberg, F]] | + | [[Category: Zetterberg F]] |
| - | [[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
The design of small and high-affinity lectin inhibitors remains a major challenge because the natural ligand binding sites of lectin are often shallow and have polar character. Herein we report that derivatizing galactose with un-natural structural elements that form multiple non-natural lectin-ligand interactions (orthogonal multipolar fluorine-amide, phenyl-arginine, sulfur-pi, and halogen bond) can provide inhibitors with extraordinary affinity (low nanomolar) for the model lectin, galectin-3, which is more than five orders of magnitude higher than the parent galactose; moreover, is selective over other galectins.
Monosaccharide Derivatives with Low-Nanomolar Lectin Affinity and High Selectivity Based on Combined Fluorine-Amide, Phenyl-Arginine, Sulfur-pi, and Halogen Bond Interactions.,Zetterberg FR, Peterson K, Johnsson RE, Brimert T, Hakansson M, Logan DT, Leffler H, Nilsson UJ ChemMedChem. 2018 Jan 22;13(2):133-137. doi: 10.1002/cmdc.201700744. Epub 2018, Jan 15. PMID:29194992[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
- ↑ Zetterberg FR, Peterson K, Johnsson RE, Brimert T, Hakansson M, Logan DT, Leffler H, Nilsson UJ. Monosaccharide Derivatives with Low-Nanomolar Lectin Affinity and High Selectivity Based on Combined Fluorine-Amide, Phenyl-Arginine, Sulfur-pi, and Halogen Bond Interactions. ChemMedChem. 2018 Jan 22;13(2):133-137. doi: 10.1002/cmdc.201700744. Epub 2018, Jan 15. PMID:29194992 doi:http://dx.doi.org/10.1002/cmdc.201700744
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