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5e8a

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Revision as of 06:47, 22 April 2020

Crystal structure of Human galectin-3 CRD in complex with 4-fluophenyl-1,2,3-triazolyl thiodigalactoside inhibitor

Structural highlights

5e8a is a 1 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
Related:	5e89, 5e88
Gene:	LGALS3, MAC2 (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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

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^[4]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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
↑ 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. Galectin-3-Binding Glycomimetics that Strongly Reduce Bleomycin-Induced Lung Fibrosis and Modulate Intracellular Glycan Recognition. Chembiochem. 2016 Jun 29. doi: 10.1002/cbic.201600285. PMID:27356186 doi:http://dx.doi.org/10.1002/cbic.201600285

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/5e8a"

@@ Line 1: / Line 1: @@
 ==Crystal structure of Human galectin-3 CRD in complex with 4-fluophenyl-1,2,3-triazolyl thiodigalactoside inhibitor==
-<StructureSection load='5e8a' size='340' side='right' caption='[[5e8a]], [[Resolution|resolution]] 1.50&Aring;' scene=''>
+<StructureSection load='5e8a' size='340' side='right'caption='[[5e8a]], [[Resolution|resolution]] 1.50&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5e8a]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5E8A OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5E8A FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5e8a]] 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=5E8A OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5E8A FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=5KS:3-DEOXY-3-[4-(4-FLUOROPHENYL)-1H-1,2,3-TRIAZOL-1-YL]-BETA-D-GALACTOPYRANOSYL+3-DEOXY-3-[4-(4-FLUOROPHENYL)-1H-1,2,3-TRIAZOL-1-YL]-1-THIO-BETA-D-GALACTOPYRANOSIDE'>5KS</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene></td></tr>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=5KS:3-DEOXY-3-[4-(4-FLUOROPHENYL)-1H-1,2,3-TRIAZOL-1-YL]-BETA-D-GALACTOPYRANOSYL+3-DEOXY-3-[4-(4-FLUOROPHENYL)-1H-1,2,3-TRIAZOL-1-YL]-1-THIO-BETA-D-GALACTOPYRANOSIDE'>5KS</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">[[5e89|5e89]], [[5e88|5e88]]</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=5e8a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5e8a OCA], [http://pdbe.org/5e8a PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5e8a RCSB], [http://www.ebi.ac.uk/pdbsum/5e8a PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5e8a ProSAT]</span></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='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=5e8a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5e8a OCA], [http://pdbe.org/5e8a PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5e8a RCSB], [http://www.ebi.ac.uk/pdbsum/5e8a PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5e8a ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 19: / Line 20: @@
 </div>
 <div class="pdbe-citations 5e8a" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Galectin 3D structures|Galectin 3D structures]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
+[[Category: Human]]
+[[Category: Large Structures]]
 [[Category: Blanchard, H]]
 [[Category: Collins, P M]]

5e8a

From Proteopedia

Revision as of 06:47, 22 April 2020

Crystal structure of Human galectin-3 CRD in complex with 4-fluophenyl-1,2,3-triazolyl thiodigalactoside inhibitor

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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