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| | ==Galectin-3C in complex with substituted polyfluoroaryl monothiogalactoside derivative 5== | | ==Galectin-3C in complex with substituted polyfluoroaryl monothiogalactoside derivative 5== |
| - | <StructureSection load='6i78' size='340' side='right' caption='[[6i78]], [[Resolution|resolution]] 1.15Å' scene=''> | + | <StructureSection load='6i78' size='340' side='right'caption='[[6i78]], [[Resolution|resolution]] 1.15Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6i78]] 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=6I78 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6I78 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6i78]] 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=6I78 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6I78 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=H5H:(2~{R},3~{R},4~{S},5~{R},6~{S})-2-(hydroxymethyl)-6-(4-methylphenyl)sulfanyl-4-[4-[2,3,5,6-tetrakis(fluoranyl)-4-(methylamino)phenyl]-1,2,3-triazol-1-yl]oxane-3,5-diol'>H5H</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]] 1.15Å</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=H5H:(2~{R},3~{R},4~{S},5~{R},6~{S})-2-(hydroxymethyl)-6-(4-methylphenyl)sulfanyl-4-[4-[2,3,5,6-tetrakis(fluoranyl)-4-(methylamino)phenyl]-1,2,3-triazol-1-yl]oxane-3,5-diol'>H5H</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=6i78 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6i78 OCA], [http://pdbe.org/6i78 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6i78 RCSB], [http://www.ebi.ac.uk/pdbsum/6i78 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6i78 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=6i78 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6i78 OCA], [https://pdbe.org/6i78 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6i78 RCSB], [https://www.ebi.ac.uk/pdbsum/6i78 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6i78 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 6i78" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 6i78" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Galectin 3D structures|Galectin 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Kumar, R]] | + | [[Category: Large Structures]] |
| - | [[Category: Logan, D T]] | + | [[Category: Kumar R]] |
| - | [[Category: Nilsson, U J]] | + | [[Category: Logan DT]] |
| - | [[Category: Peterson, K]] | + | [[Category: Nilsson UJ]] |
| - | [[Category: Carbohydrate-binding protein]] | + | [[Category: Peterson K]] |
| - | [[Category: Galactose-specific lectin 3]]
| + | |
| - | [[Category: Galactoside-binding protein]]
| + | |
| - | [[Category: Galbp]]
| + | |
| - | [[Category: Ige-6 binding protein]]
| + | |
| - | [[Category: L-31]]
| + | |
| - | [[Category: Laminin-binding protein]]
| + | |
| - | [[Category: Lectin]]
| + | |
| - | [[Category: Lectin l-29]]
| + | |
| - | [[Category: Mac-2]]
| + | |
| - | [[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
In the beta-d-galactopyranoside-binding protein galectin-3, synthetic inhibitors substituted at the 3-position of a thiodigalactoside core cause the formation of an aglycone binding pocket through the displacement of an arginine residue (Arg144) from its position in the apoprotein. To examine in detail the role of different molecular interactions in this pocket, we have synthesized a series of nine 3-(4-(2,3,5,6-tetrafluorophenyl)-1,2,3-triazol-1-yl)-thiogalactosides with different para substituents and measured their affinities to galectin-3 using a fluorescence polarization assay. High-resolution crystal structures (<1.3 A) have been determined for five of the ligands in complex with the C-terminal domain of galectin-3. The binding affinities are rationalised with the help of the three-dimensional structures and quantum-mechanical calculations. Three effects seem to be involved: Firstly, the binding pocket is too small for the largest ligands with ethyl and methyl. Secondly, for the other ligands, the affinity seems to be determined mainly by desolvation effects, disfavouring the polar substituents, but this is partly counteracted by the cation-pi interaction with Arg144, which stacks on top of the substituted tetrafluorophenyl group in all complexes. The results provide detailed insight into interactions of fluorinated phenyl moieties with arginine-containing protein binding sites and the complex interplay of different energetic components in defining the binding affinity.
Substituted polyfluoroaryl interactions with an arginine side chain in galectin-3 are governed by steric-, desolvation and electronic conjugation effects.,Kumar R, Peterson K, Misini Ignjatovic M, Leffler H, Ryde U, Nilsson UJ, Logan DT Org Biomol Chem. 2019 Jan 31;17(5):1081-1089. doi: 10.1039/c8ob02888e. PMID:30632578[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
- ↑ Kumar R, Peterson K, Misini Ignjatovic M, Leffler H, Ryde U, Nilsson UJ, Logan DT. Substituted polyfluoroaryl interactions with an arginine side chain in galectin-3 are governed by steric-, desolvation and electronic conjugation effects. Org Biomol Chem. 2019 Jan 31;17(5):1081-1089. doi: 10.1039/c8ob02888e. PMID:30632578 doi:http://dx.doi.org/10.1039/c8ob02888e
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